Tokala, Ramya published the artcileDevelopment of β-carboline-benzothiazole hybrids via carboxamide formation as cytotoxic agents: DNA intercalative topoisomerase IIα inhibition and apoptosis induction, Computed Properties of 95-24-9, the publication is Bioorganic Chemistry (2021), 104481, database is CAplus and MEDLINE.
In quest of promising anticancer agents, the pharmacophores of natural (β-carboline) and synthetic origin (benzothiazole) were adjoined by a carboxamide bridge and three-point diversification was accomplished. The in vitro cytotoxic ability of the compounds was established on adherent and suspension human cancer cell lines and compounds I and II advanced as pre-eminent mols. with IC50 values of 1.46 and 1.81μM resp. in A549 cell line. The cytospecificity was entrenched for potent compounds I and II by evaluating against normal human lung epithelial cells and selectivity index was calculated Furthermore, EtBr displacement, relative viscosity and gel-based topoisomerase II target assays unveiled the intercalative topo-II inhibitory capability and DNA binding studies (absorbance) revealed the dissociation constant (Kd) for compounds I and II as 98 and 103μM resp. Addnl., cell-based flow cytometric assays like Annexin-V/PI dual staining aids in the quantification of apoptosis induced and JC-1 staining disclosed the depolarization of mitochondrial membrane potential by compound I in A549 cells in a dose-dependent manner. Moreover, wound healing assay established the inhibition of in vitro cell migration by compound I on A549 cells. In addition, mol. docking studies proved the binding of compounds I and II in the active site of DNA complexed with topo IIα and stabilized by interactions with DNA base pairs and amino acid residues. Remarkably, the compounds I and II follow Lipinski’s rule of five and are in the recommended range for Jorgensen’s rule of three with a minimal violation and other pharmacokinetic parameters revealing druggability of the synthesized hybrids.
Bioorganic Chemistry published new progress about 95-24-9. 95-24-9 belongs to thiazole, auxiliary class Organic Pigment, name is 6-Chlorobenzothiazol-2-ylamine, and the molecular formula is C30H42NOP, Computed Properties of 95-24-9.
Referemce:
https://pubchem.ncbi.nlm.nih.gov/compound/thiazole,
Thiazole | chemical compound | Britannica