Day: November 22, 2022

Bee venom-loaded EGFR-targeting peptide-coupled chitosan nanoparticles for effective therapy of hepatocellular carcinoma by inhibiting EGFR-mediated MEK/ERK pathway was written by Abdulmalek, Shaymaa;Mostafa, Nouf;Gomaa, Marwa;El-Kersh, Mohamed;Elkady, Ayman I.;Balbaa, Mahmoud. And the article was included in PLoS One in 2022.Category: thiazole The following contents are mentioned in the article:

Hepatocellular carcinoma (HCC) is one of the world′s most risky diseases due to the lack of clear and cost-effective therapeutic targets. Currently, the toxicity of conventional chemotherapeutic medications and the development of multidrug resistance is driving research into targeted therapies. The nano-biomedical field′s potential for developing an effective therapeutic nano-sized drug delivery system is viewed as a significant pharmaceutical trend for the encapsulation and release of numerous anticancer therapies. In this regard, current research is centered on the creation of biodegradable chitosan nanoparticles (CSNPs) for the selective and sustained release of bee venom into liver cancer cells. Furthermore, surface modification with polyethylene glycol (PEG) and GE11 peptide-conjugated bee venom-CSNPs allows for the targeting of EGFR-overexpressed liver cancer cells. A series of in vitro and in vivo cellular analyses were used to investigate the antitumor effects and mechanisms of targeted bee venom-CSNPs. Targeted bee venom-CSNPs, in particular, were found to have higher cytotoxicity against HepG2 cells than SMMC-7721 cells, as well as stronger cellular uptake and a substantial reduction in cell migration, leading to improved cancer suppression. It also promotes cancer cell death in EGFR overexpressed HepG2 cells by boosting reactive oxygen species, activating mitochondria-dependent pathways, inhibiting EGFR-stimulated MEK/ERK pathway, and elevating p38-MAPK in comparison to native bee venom. In hepatocellular carcinoma (HCC)-induced mice, it has anti-cancer properties against tumor tissue. It also improved liver function and architecture without causing any noticeable toxic side effects, as well as inhibiting tumor growth by activating the apoptotic pathway. The design of this cancer-targeted nanoparticle establishes GE11-bee venom-CSNPs as a potential chemotherapeutic treatment for EGFR over-expressed malignancies. Finally, our work elucidates the mol. mechanism underlying the anticancer selectivity of targeted bee venom-CSNPs and outlines therapeutic strategies to target liver cancer. This study involved multiple reactions and reactants, such as 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0Category: thiazole).

3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0) belongs to thiazole derivatives. Thiazoles in peptides or their ability to bind proteins, DNA and RNA has led to many synthetic studies and new applications. Thiazole sulfonation occurs only under forcing conditions: the action of oleum at 250 °C for 3 hours in the presence of mercury(II) sulfate leads to 65% formation of 5-thiazole sulfonic acid.Category: thiazole

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Development of bioactive catechol functionalized nanoparticles applicable for 3D bioprinting was written by Puertas-Bartolome, Maria;Wlodarczyk-Biegun, Malgorzata K.;del Campo, Aranzazu;Vazquez-Lasa, Blanca;San Roman, Julio. And the article was included in Materials Science & Engineering in 2021.HPLC of Formula: 38215-36-0 The following contents are mentioned in the article:

Efficient wound treatments to target specific events in the healing process of chronic wounds constitute a significant aim in regenerative medicine. In this sense, nanomedicine can offer new opportunities to improve the effectiveness of existing wound therapies. The aim of this study was to develop catechol bearing polymeric nanoparticles (NPs) and to evaluate their potential in the field of wound healing. Thus, NPs wound healing promoting activities, potential for drug encapsulation and controlled release, and further incorporation in a hydrogel bioink formulation to fabricate cell-laden 3D scaffolds are studied. NPs with 2 and 29 M % catechol contents (named NP2 and NP29) were obtained by nanopptn. and presented hydrodynamic diameters of 100 and 75 nm resp. These nanocarriers encapsulated the hydrophobic compound coumarin-6 with 70% encapsulation efficiency values. In cell culture studies, the NPs had a protective effect in RAW 264.7 macrophages against oxidative stress damage induced by radical oxygen species (ROS). They also presented a regulatory effect on the inflammatory response of stimulated macrophages and promoted upregulation of the vascular endothelial growth factor (VEGF) in fibroblasts and endothelial cells. In particular, NP29 were used in a hydrogel bioink formulation using carboxymethyl chitosan and hyaluronic acid as polymeric matrixes. Using a reactive mixing bioprinting approach, NP-loaded hydrogel scaffolds with good structural integrity, shape fidelity and homogeneous NPs dispersion, were obtained. The in vitro catechol NPs release profile of the printed scaffolds revealed a sustained delivery. The bioprinted scaffolds supported viability and proliferation of encapsulated L929 fibroblasts over 14 days. We envision that the catechol functionalized NPs and resulting bioactive bioink presented in this work offer promising advantages for wound healing applications, as they: 1 support controlled release of bioactive catechol NPs to the wound site; 2 can incorporate addnl. therapeutic functions by co-encapsulating drugs; 3 can be printed into 3D scaffolds with tailored geometries based on patient requirements. This study involved multiple reactions and reactants, such as 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0HPLC of Formula: 38215-36-0).

3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.HPLC of Formula: 38215-36-0

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Deficiency of telomere-associated repressor activator protein 1 precipitates cardiac aging in mice via p53/PPARα signaling was written by Cai, Yin;Liu, Hao;Song, Erfei;Wang, Lin;Xu, Jindong;He, Yi;Zhang, Dengwen;Zhang, Liyan;Cheng, Kenneth King-yip;Jin, Leigang;Wu, Min;Liu, Shiming;Qi, Dake;Zhang, Liangqing;Lopaschuk, Gary D.;Wang, Sheng;Xu, Aimin;Xia, Zhengyuan. And the article was included in Theranostics in 2021.Reference of 63208-82-2 The following contents are mentioned in the article:

Telomere shortening and dysfunction may cause metabolic disorders, tissue damage and age-dependent pathologies. However, little is known about the association of telomere-associated protein Rap1 with mitochondrial energy metabolism and cardiac aging. Echocardiog. was performed to detect cardiac structure and function in Rap1^+/+ and Rap1^-/- mice at different ages (3 mo, 12 mo and 20 mo). Telomere length, DNA damage, cardiac senescence and cardiomyocyte size were analyzed using the real-time PCR, Western blotting, senescence associated β-galactosidase assay and wheat germ agglutinin staining, resp. Western blotting was also used to determine the level of cardiac fatty acid metabolism related key enzymes in mouse and human myocardium. Chromatin immunoprecipitation assay was used to verify the direct link between p53 and PPARα. The p53 inhibitor, Pifithrin-α and PPARα activator WY14643 were utilized to identify the effects of Rap1/p53/PPARα signaling pathway. Telomere was shortened concomitant with extensive DNA damage in aged Rap1^-/- mouse hearts, evidenced by reduced T/S ratios and increased nuclear γH2AX. Meanwhile, the aging-associated phenotypes were pronounced as reflected by altered mitochondrial ultrastructure, enhanced senescence, cardiac hypertrophy and dysfunction. Mechanistically, acetylated p53 and nuclear p53 was enhanced in the Rap1^-/- mouse hearts, concomitant with reduced PPARα. Importantly, p53 directly binds to the promoter of PPARα in mouse hearts and suppresses the transcription of PPARα. In addition, aged Rap1^-/- mice exhibited reduced cardiac fatty acid metabolism Pifithrin-α alleviated cardiac aging and enhanced fatty acid metabolism in the aged Rap1^-/- mice. Activating PPARα with WY14643 in primarily cultured Rap1^-/- cardiomyocytes restored maximal oxygen consumption rates. Reduced Rap1 expression and impaired p53/PPARα signaling also presented in aged human myocardium. In summary, Rap1 may link telomere biol. to fatty acid metabolism and aging-related cardiac pathologies via modulating the p53/PPARα signaling pathway, which could represent a therapeutic target in preventing/attenuating cardiac aging. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Reference of 63208-82-2).

2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazole is a five-membered, unsaturated, planar, π-excessive heteroaromatic containing one sulfur atom and one pyridine-type nitrogen atom at position 3 of the cyclic ring system. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.Reference of 63208-82-2

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Isoquercitrin protects HUVECs against high glucose-induced apoptosis through regulating p53 proteasomal degradation was written by Liu, Libo;Huang, Sihui;Xu, Man;Gong, Yan;Li, Dan;Wan, Chunxia;Wu, Haiming;Tang, Qizhu. And the article was included in International Journal of Molecular Medicine in 2021.COA of Formula: C16H19BrN2OS The following contents are mentioned in the article:

High glucose (HG)-induced endothelial apoptosis serves an important role in the vascular dysfunction associated with diabetes mellitus (DM). It has been reported that isoquer- citrin (IQC), a flavonoid glucoside, possesses an anti-DM effect, but the mechanism requires further investigation. The present study investigated the effect of IQC against HG-induced apop- tosis in human umbilical vein endothelial cells (HUVECs) and explored its mol. mechanism. HUVECs were treated with 5 or 30 mM glucose for 48 h. Endothelial cell viability was monitored using the Cell Counting Kit-8 assay. Mitochondrial membrane potential was detected by JC-1 staining. Apoptosis was observed by TUNEL staining and flow cytometry. Western blotting was used for the anal. of apoptosis-associated proteins Bax, Bcl-2, cleaved (C)-caspase3, total-caspase3, p53 and phosphorylated p53. Reverse transcription-quant. PCR was used to analyze the mRNA expression levels of Bax, Bcl-2 and p53. Immunofluorescence staining was utilized to detect the expression levels and distribution of p53 and ubiquitin specific peptidase 10 (USP10) in HUVECs. The results revealed that IQC significantly attenuated HG-induced endothelial apoptosis, as shown by decreased apoptotic cells observed by TUNEL, JC-1 staining and flow cytometry. Moreover, under HG stress, IQC treatment markedly inhibited the increased expression levels of the pro-apoptotic proteins p53, Bax and C-caspase3, and increased the expression levels of the anti-apoptotic protein Bcl-2 in HUVECs. However, the anti-apoptotic effect of IQC against HG was partially blunted by increasing p53 protein levels in vitro. IQC influenced the mRNA expression levels of Bax and Bcl-2 in response to HG, but it did not affect the transcription of p53. Notably, IQC inhib-ited the HG-induced phosphorylation of p53 at Ser15 and the nuclear transport of USP10, destabilizing p53 and increasing the proteasomal degradation of the p53 protein. The current findings revealed that IQC exerted a protective effect against the HG-induced apoptosis of endothelial cells by regulating the proteasomal degradation of the p53 protein, suggesting that IQC may be used as a novel therapeutic compound to ameliorate DM-induced vascular complications. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2COA of Formula: C16H19BrN2OS).

2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Thiazole is a versatile building block for the construction and lead generation of new drug discoveries. Numerous diazole-based compounds are in clinical use as anticancer, antileukemic, antiinflammatory, antiviral, antifungal, antirheumatic, immunomodulator, and antiparasitic agents.COA of Formula: C16H19BrN2OS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

New heterocyclic modifiers of oxidative drug metabolism. I. 6-Substituted-2-aminobenzothiazoles was written by Murray, Michael;Lacey, Ernest;Farrell, Geoffrey C.. And the article was included in Biochemical Pharmacology in 1986.Computed Properties of C11H14N2OS The following contents are mentioned in the article:

A series of 6-substituted-2-aminobenzothiazoles(2-AB) I (R = H, alkoxy, halo, etc.) was synthesized and evaluated as in vitro inhibitors of microsomal mixed-function oxidase  [9038-14-6] activity (as aminopyrine N-demethylase  [9037-69-8]) from phenobarbitone-induced rat liver. Using physiochem. parameters and multiple regression anal., QSAR was derived in which 82% of the data variance was accounted for in terms of the hydrophobic character of the inhibitor and the molar refractivity of the 2-AB 6-substituent. In contrast, literature equations derived from earlier studies with heterocyclic systems possessing nonpolar substituents underestimated by up to an order of magnitude the potency of the present compounds Kinetic studies revealed the 6-n-propoxy-2-AB, one of the more potent compounds, was a pure competitive inhibitor of aminopyrine N-demethylase activity (K_i = 60 μM from Dixon anal.), suggesting the the binding of substrate and inhibitor is mutually exclusive at the cytochrome P 450  [9035-51-2] active site. Binding studies indicated that most 2-AB derivatives elicited mixed-type I-reverse type I optical difference spectra in phenobarbitone-induced microsomes. The overlap of these components resulted in nonlinear double reciprocal plots of the spectral titrations and precluded the determination of binding parameters. In contrast, the more potent inhibitors (the 6-propoxy and 6-butoxy derivatives of 2-AB) were type I ligands with quite high affinity for ferric cytochrome P 450. Although no quant. relationship was apparent between inhibition and spectral binding affinity, a good correlation was observed between inhibition potency (I₅₀) and the capacity of 10 2-AB derivatives to prevent substrate (aminoipyrine) binding to cytochrome P 450. These findings suggest that 2-AB derivatives may inhibit microsomal oxidation via a direct competitive effect on substrate binding to cytochrome P 450. The present study also demonstrates that substitution of heterocyclic systems with hydrophilic groups does not necessarily produce weak inhibitors of mixed-function oxidase activity, and that extrapolation of existing QSAR equations to new inhibitor series must be interpreted with caution. This study involved multiple reactions and reactants, such as 6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7Computed Properties of C11H14N2OS).

6-Butoxybenzo[d]thiazol-2-amine (cas: 14372-65-7) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Computed Properties of C11H14N2OS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

New heterocyclic modifiers of oxidative drug metabolism. I. 6-Substituted-2-aminobenzothiazoles was written by Murray, Michael;Lacey, Ernest;Farrell, Geoffrey C.. And the article was included in Biochemical Pharmacology in 1986.COA of Formula: C10H12N2OS The following contents are mentioned in the article:

A series of 6-substituted-2-aminobenzothiazoles(2-AB) I (R = H, alkoxy, halo, etc.) was synthesized and evaluated as in vitro inhibitors of microsomal mixed-function oxidase  [9038-14-6] activity (as aminopyrine N-demethylase  [9037-69-8]) from phenobarbitone-induced rat liver. Using physiochem. parameters and multiple regression anal., QSAR was derived in which 82% of the data variance was accounted for in terms of the hydrophobic character of the inhibitor and the molar refractivity of the 2-AB 6-substituent. In contrast, literature equations derived from earlier studies with heterocyclic systems possessing nonpolar substituents underestimated by up to an order of magnitude the potency of the present compounds Kinetic studies revealed the 6-n-propoxy-2-AB, one of the more potent compounds, was a pure competitive inhibitor of aminopyrine N-demethylase activity (K_i = 60 μM from Dixon anal.), suggesting the the binding of substrate and inhibitor is mutually exclusive at the cytochrome P 450  [9035-51-2] active site. Binding studies indicated that most 2-AB derivatives elicited mixed-type I-reverse type I optical difference spectra in phenobarbitone-induced microsomes. The overlap of these components resulted in nonlinear double reciprocal plots of the spectral titrations and precluded the determination of binding parameters. In contrast, the more potent inhibitors (the 6-propoxy and 6-butoxy derivatives of 2-AB) were type I ligands with quite high affinity for ferric cytochrome P 450. Although no quant. relationship was apparent between inhibition and spectral binding affinity, a good correlation was observed between inhibition potency (I₅₀) and the capacity of 10 2-AB derivatives to prevent substrate (aminoipyrine) binding to cytochrome P 450. These findings suggest that 2-AB derivatives may inhibit microsomal oxidation via a direct competitive effect on substrate binding to cytochrome P 450. The present study also demonstrates that substitution of heterocyclic systems with hydrophilic groups does not necessarily produce weak inhibitors of mixed-function oxidase activity, and that extrapolation of existing QSAR equations to new inhibitor series must be interpreted with caution. This study involved multiple reactions and reactants, such as 6-Isopropoxybenzo[d]thiazol-2-amine (cas: 15850-81-4COA of Formula: C10H12N2OS).

6-Isopropoxybenzo[d]thiazol-2-amine (cas: 15850-81-4) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.COA of Formula: C10H12N2OS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

α-Synucleinopathy associated c-Abl activation causes p53-dependent autophagy impairment was written by Karim, Razaul Md.;Liao, Elly E.;Kim, Jaekwang;Meints, Joyce;Martinez, Hector Martell;Pletnikova, Olga;Troncoso, Juan C.;Lee, Michael K.. And the article was included in Molecular Neurodegeneration in 2020.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide The following contents are mentioned in the article:

Abstract: Background: Studies link c-Abl activation with the accumulation of pathogenic α-synuclein (αS) and neurodegeneration in Parkinson’s disease (PD). Currently, c-Abl, a tyrosine kinase activated by cellular stress, is thought to promote αS pathol. by either directly phosphorylating αS or by causing autophagy deficits. Methods: αS overexpressing transgenic (Tg) mice were used in this study. A53T Tg mice that express high levels of human mutant A53TαS under the control of prion protein promoter. Two different approaches were used in this study. Natural aging and seeding model of synucleinopathy. In seeding model, intracortical/intrastriatal (IC/IS) stereotaxic injection of toxic lysates was done using tissue lysates from end-stage symptomatic mice. In this study, nilotinib and pifithrin-α was used as a c-Abl and p53 inhibitor, resp. Both Tg and non-transgenic (nTg) mice from each group were subjected to nilotinib (10 mg/kg) or vehicle (DMSO) treatment. Frozen brain tissues from PD and control human cases were analyzed. In vitro cells study was implied for c-Abl/p53 genetic manipulation to uncover signal transduction. Results: Herein, we show that the pathol. effects of c-Abl in PD also involve activation of p53, as c-Abl activation in a transgenic mouse model of α-synucleinopathy (TgA53T) and human PD cases are associated with the increased p53 activation. Significantly, active p53 in TgA53T neurons accumulates in the cytosol, which may lead to inhibition of autophagy. Thus, we hypothesized that c-Abl-dependent p53 activation contributes to autophagy impairment in α-synucleinopathy. In support of the hypothesis, we show that c-Abl activation is sufficient to inhibit autophagy in p53-dependent manner. Moreover, inhibition of either c-Abl, using nilotinib, or p53, using pifithrin-α, was sufficient to increase autophagic flux in neuronal cells by inducing phosphorylation of AMP-activated kinase (AMPK), ULK1 activation, and down-regulation of mTORC1 signaling. Finally, we show that pharmacol. attenuation of c-Abl activity by nilotinib treatment in the TgA53T mouse model reduces activation of p53, stimulates autophagy, decreases accumulation αS pathol., and delays disease onset. Conclusion: Collectively, our data show that c-Abl activation by α-synucleinopathy causes p53 dependent autophagy deficits and both c-Abl and p53 represent therapeutic target for PD. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide).

2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles are a class of five-membered rings containing nitrogen and sulfur with excellent antitumor, antiviral and antibiotic activities. Electrophilic attack at nitrogen depends on the presence of electron density at nitrogen as well as the position and nature of substituent linked to the thiazole ring.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Sirt-1 regulates physiological process and exerts protective effects against oxidative stress was written by Liu, Lei;Xia, Guangyuan;Li, Peifan;Wang, Yiming;Zhao, Qian. And the article was included in BioMed Research International in 2021.Formula: C16H19BrN2OS The following contents are mentioned in the article:

Recent studies suggest a correlation between the reduced Sirt-1 expression with Alzheimer’s diseases (AD) and depression, resp., suggesting a possible pathogenic role of the altered Sirt-1 expression in neuronal degenerative diseases, such as AD and depression. However, the mol. mechanisms underlying how Sirt-1 reduction impairs neuronal functions remain unknown. We used the SK-N-SH neuroblastoma cells to study the role of Sirt-1 expression on physiol. roles in neuronal cells. Gain of Sirt-1 was achieved by transiently transfecting Sirt-1 expression plasmid. Sirt-1-specific shRNA was used to elucidate the role of Sirt-1 loss of function. CCK-8 (Cell Counting Kit-8) assay and flow cytometry were used to evaluate cell proliferation. Semiquant. western blotting was used to detect relative protein levels. A further luciferase reporter gene assay was employed to examine the effect of Sirt-1 expression on the transcriptional activity of p53. RT-qPCR was used to determine the mRNA levels of p21, Bax, and Bcl-2, which were the downstream target genes of p53. Sirt-1 suppressed the p53 downstream gene p21 transcription, while shRNA-mediated Sirt-1 knockdown resulted in a significant increase in p21 expression, implying a possibility that Sirt-1 promotes neuron proliferation through suppressing p53 transcriptional activity. The mRNA and protein levels of p53 were not affected by the altered Sirt-1 expression, suggesting that Sirt-1 regulates the transcriptional regulatory activity of p53 rather than p53 expression. Indeed, we further confirmed that Sirt-1 appeared to inhibit p53 transcriptional activity by attenuating its acetylation and resulted in a decrease of p53’s binding to the p21 promoter. Overexpressed Sirt-1 scavenged reactive oxygen species (ROS) production in SK-N-SH with H2O2. Knockdown of Sirt-1 presented opposite effect; the addition of EX527 (Sirt-1 inhibitor) increased ROS accumulation. Oxidative stress induces Sirt-1 in neuron cells, and Sirt-1 promotes proliferation in SK-N-SH cells, which protects them from oxidative stress-induced cell death, potentially via suppressing the transcriptional activity of p53. These results provide a mol. explanation underlying how the reduced Sirt-1 potentially causes the AD and depression-related diseases, supporting the idea that Sirt-1 can possibly be used as a diagnostic biomarker and/or therapeutic drug target for the AD and depression-related diseases. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Formula: C16H19BrN2OS).

2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). The nitrogen in thiazole is sp2 hybridized and the lone pair of electrons localized on the nitrogen is less reactive due to increased aromatic character and decreased basicity. It is protonated and alkylated/acylated at nitrogen forming hydrochloride and quaternary thiazolium salt.Formula: C16H19BrN2OS

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

To investigate fit-to-purpose nanocarrier for non-invasive drug delivery to posterior segment of eye was written by Tambe, Vishakha;Raval, Nidhi;Gondaliya, Piyush;Bhattacharya, Pallab;Kalia, Kiran;Tekade, Rakesh Kumar. And the article was included in Journal of Drug Delivery Science and Technology in 2021.Reference of 38215-36-0 The following contents are mentioned in the article:

Diseases of the posterior segment of the eye are difficult to treat due to lesser bioavailability of therapeutics at the posterior segment of the eye. Current clin. interventions involve administering drugs via invasive routes (Intravitreal, Retrobulbar, or Peribulbar) that bear the least patient compliance. Several nanocarriers strategies have shown a remarkable potential to deliver the loaded therapeutic to the posterior tissues of the eye. However, no one platform report was available to demarcate the most effective delivery system out of the recommended approaches. This investigation aimed at exploring a suitable and efficient non-invasive topically administrable nanocarriers system for the delivery of the drug to the posterior segment of the eye. Dexamethasone (DEX, a corticosteroid used for ocular inflammation) was selected as a model drug. The nanocarriers were formulated (size ∼ 120 nm) and studied their potential at a common platform to deliver the drug to the posterior segment of the eye. The nanocarriers were analyzed for their in vitro drug release profile in simulated tear fluid (STF) depicting sustained release of DEX up to 24 h, ex-vivo corneal permeability, using excised goat cornea, cytotoxicity potential using human retinal pigment epithelium ARPE-19 cell lines, HET CAM assay to evaluate ocular irritancy, elec. resistance measurement across monolayers of Rabbit corneal epithelial cells SIRC and ARPE-19 cells and stability profiles, real-time qPCR IL-6 gene expression in ARPE-19 inflammation model. Ex-vivo corneal permeability demonstrated that the highest percentage of DEX was permeated by DEX-NLCs and lowest by DEX-SLNs. All the nanocarriers except DEX-CUBs depicted no cytotoxicity in ARPE-19 cells. All the nanocarriers depicted the change in elec. resistance measurement across monolayers of Rabbit corneal epithelial cells SIRC and ARPE-19 cells. They were also found to reduce the levels of IL-6 in gene expression assay depicting successful in vitro delivery to ARPE-19 cells. However, only NLCs and NMFs were selected further as they demonstrated better potential to permeate after ex vivo and in vitro permeability studies. Further, in-vivo fluorescence imaging studies in Wistar rats were also performed with coumarin-6 loaded nanocarriers to deduce the effective and suitable candidate to deliver a drug to the posterior segment of the eye with the highest biosafety and permeability. This study involved multiple reactions and reactants, such as 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0Reference of 38215-36-0).

3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0) belongs to thiazole derivatives. The thiazole ring is notable as a component of the vitamin thiamine (B1). There are numerous natural products that possess a thiazole ring with broad pharmacological activities. Thiamine, also known as vitamin B1, possesses a thiazole ring linked with 2-methylpyrimidine-4-amine as hydrochloride salt.Reference of 38215-36-0

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica

Serine mutations in overexpressed Hsp27 abrogate the protection against doxorubicin-induced p53-dependent cardiac apoptosis in mice was written by Kanagasabai, Ragu;Karthikeyan, Krishnamurthy;Zweier, Jay L.;Ilangovan, Govindasamy. And the article was included in American Journal of Physiology in 2021.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide The following contents are mentioned in the article:

Small heat shock proteins (sHsps) protect the heart from chemotherapeutics-induced heart failure by inhibiting p53-dependent apoptosis. However, mechanism of such protection has not been elucidated yet. Here we test a hypothesis that serine phosphorylation of sHsps is essential to inhibit the doxorubicin-induced and p53-dependent apoptotic pathway. Three transgenic mice (TG) lines with cardiomyocyte-specific overexpression of human heat shock protein 27 (hHsp27), namely, wild-type [myosin heavy chain (MHC)-hHsp27], S82A single mutant [MHC-mut-hHsp27(S82A)], and trimutant [MHC-mut-hHsp27(S15A/S78A/S82A)] were generated. TG mice were treated with Dox (6 mg/kg body wt; once in a week; 4 wk) along with age-matched nontransgenic (non-TG) controls. The Doxtreated MHC-hHsp27 mice showed improved survival and cardiac function (both MRI and echocardiog.) in terms of contractility [ejection fraction (%EF)] and left ventricular inner diameter (LVID) compared with the Dox-treated non-TG mice. However, both MHCmut-hHsp27(S82A) and MHC-mut-hHsp27(S15A/S78A/S82A) mutants overexpressing TG mice did not show such a cardioprotection. Furthermore, transactivation of p53 was found to be attenuated only in Dox-treated MHC-hHsp27 mice-derived cardiomyocytes in vitro, as low p53 was detected in the nuclei, not in mutant hHsp27 overexpressing cardiomyocytes. Similarly, only in MHC-hHsp27 overexpressing cardiomyocytes, low Bax, higher mechanistic target of rapamycin (mTOR) phosphorylation, and low apoptotic poly (ADP-ribose) polymerase-1 (PARP-1) cleavage (89 kDa fragment) were detected. Pharmacol. inhibition of p53 was more effective in mutant TG mice compared with MHC-hHsp27 mice. We conclude that phosphorylation of overexpressed Hsp27 at S82 and its association with p53 are essential for the cardioprotective effect of overexpressed Hsp27 against Dox-induced dilated cardiomyopathy. Only phosphorylated Hsp27 protects the heart by inhibiting p53 transactivation. NEW & NOTEWORTHY Requirement of serine phosphorylation in Hsp27 for cardioprotective effect against Dox is tested in various mutants overexpressing mice. Cardioprotective effect was found to be compromised in Hsp27 serine mutants overexpressed mice compared with wild-type overexpressing mice. These results indicate that cancer patients, who carry these mutations, may have higher risk of aggravated cardiomyopathy on treated with cardiotoxic chemotherapeutics such as doxorubicin. This study involved multiple reactions and reactants, such as 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide).

2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide (cas: 63208-82-2) belongs to thiazole derivatives. Thiazoles frequently appear in peptide studies. Thiazoles can also be used as protected formyl groups, which can be released in later stages of complex natural product synthesis. The pyridine-type nitrogen in the thiazole ring deactivates the ring for electrophilic substitution reactions, which is further reduced in acid due to protonation of the thiazole ring.Name: 2-(2-Imino-4,5,6,7-tetrahydrobenzothiazol-3-yl)-1-p-tolylethanone Hydrobromide

Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica