Repurposing of Guanabenz acetate by encapsulation into long-circulating nanopolymersomes for treatment of triple-negative breast cancer was written by Haggag, Yusuf A.;Yasser, Mohamed;Tambuwala, Murtaza M.;El Tokhy, Suleiman S.;Isreb, Mohammad;Donia, Ahmed A.. And the article was included in International Journal of Pharmaceutics in 2021.Application In Synthesis of 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one The following contents are mentioned in the article:
Poor patient response and limited treatment modalities are the major challenges against combating triple-neg. breast cancer (TNBC). The high related mortality urges for novel cancer therapeutics. Guanabenz acetate (GA) is an orphan antihypertensive drug with a short half-life. Re-purposing (GA) by developing a polymersome (PS)-based cancer nanomedicine is an innovative approach in treating TNBC. Formulation and optimization of GA-loaded PEGylated Polycaprolactone PS through different process variables (solvent selection, the order of addition, pH of the aqueous phase, and drug to polymer ratio) were achieved by the nanopptn. method. The in vitro cellular uptake, anti-cancer, and anti-metastatic activity of GA and GA-loaded PS were tested in MDA-MB 231(TNBC cell line) and MCF-7 cell line. Western blot anal. was performed to elucidate the mol. anti-cancer mechanism. The in vivo biodistribution study and antitumor activity were investigated in the TNBC-xenograft model implanted in mice. Under optimized formulation conditions, GA-loaded PS had a nanosize of 90.5 nm with PDI < 0.2, a zeta potential -9.11 mV, drug encapsulation efficiency of 92.11% and sustained drug release for 6-days. GA-loaded PS exhibited enhanced cellular uptake and achieved a significantly lower IC50 in both breast cancer cell lines compared to free GA. Treatment with GA-loaded PS (60μM) showed a significant reduction of 60.5 and 78.1% in cancer migration and metastasis in the case of MDA-MB 231 and MCF-7, resp. Besides, drug-loaded PS increased phosphorylation of translational regulator eIF2α and decreased expression of Rac1 which were essential for decreasing cancer cell survival and metastasis. In vivo biodistribution study of GA-loaded PS showed long-circulating PS with high passively targeted tumor accumulation. Treatment with GA-loaded PS resulted in a significant decrease in tumor size and weight compared to free GA. In conclusion, GA-loaded PS is a new promising cancer therapeutics for the treatment of TNBC. This study involved multiple reactions and reactants, such as 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0Application In Synthesis of 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one).
3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one (cas: 38215-36-0) 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.Application In Synthesis of 3-(Benzo[d]thiazol-2-yl)-7-(diethylamino)-2H-chromen-2-one
Referemce:
Thiazole | C3H3NS – PubChem,
Thiazole | chemical compound | Britannica