To avert the menace of pathogens in medical parlance, emerging attractive strategy is combining two different active fragments in a single molecule for scientific solutions. Trisubstituted imidazo[1,2-a]pyridine-carboxylate was engrossed as a hybrid with oxadiazole. The three dimensional and crystal structures of compounds 3-[5-(2-chlorophenyl)-1,3,4-oxadiazol-(4 e) were determined using single crystal X-ray diffraction studies and their crystal packing was analyzed using Hirshfeld surface computational analysis. The molecular conformation of 4 c (planar) and 4 e (twisted) and crystal packing is different and this may be due to substitution effect. In addition, both compounds have common intermolecular interactions of the type C-H…π and intercontacts H…H contributes more to the Hishfeld surfaces. Screening for microbial activity acknowledged, 2,8-dimethyl-3-[5-(3-nitrophenyl)-1,3,4-oxadiazol-2-yl] imidazo[1,2-a]pyridine (4 f) and 6-chloro-2-methyl-3-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]imidazo[1,2-a]pyridine (4 g) as most effective against Staphyllococus aureus, over all other derivatives. Meanwhile, 4 f also showed pronounced antifungal activity against Candida albicans. Further 4 f was endorsed by time kill assay as bactericidal in its action.[a] S.
Defined with a dual‐mode of action, the hybrid molecule synthesis is an attractive strategy to endure the scientific challenges in drug discovery. Besides worthy development in cancer therapy, it is still a leading cause of death across the globe. Failure in terms of efficacy, selectivity and toxicity, the statistics of a potential drug to concrete the cancer is rather in bleak. In the present study, synthesized hybrid molecules were well characterized by spectroscopy techniques. The single‐crystal X‐ray crystallography study revealed the monoclinic crystal system of Dimethyl 1,4‐dihydro‐2,6‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐3,5‐dicarboxylate (5 b) with spacegroup C2/c. MTT assay provided the anticancer property of the compounds Diethyl1,4‐dihydro‐3,5‐dimethyl‐4‐(3‐(5‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐1H‐pyrazol‐4‐yl)pyridine‐2,6‐dicarboxylate (5 a) and 5‐methyl‐1‐phenyl‐4‐(4‐(4,5‐diphenyl‐1H‐imidazol‐2‐yl)‐1H‐pyrazol‐3‐yl)‐1H‐pyrazole (6 a) against A549 cell lines with the IC50 values of 42.79 μM and 55.13 μM respectively. The AO‐EB staining assay for cell death analysis confirmed the selective action of both 5 a and 6 a. Further, molecular docking confirmed the effective binding with cyclin‐dependent kinase (CDK2) protein, suggesting that the target compounds are remarkable inhibitors in dysregulating the CDK2 protein in cancer cells.
This study explores the synthesis of different imidazopyridine derivatives, their characterization, single crystal x-ray diffraction, molecular Hirshfeld surface analysis along with their anticancer and other supportive biological evaluations. X-ray crystallography study resolved the crystal structure of 2,7dimethyl-N-(1,3-dioxoisoindolin-2-yl)H-imidazo[1,2-a]pyridine-3carboxamide (2 a) as monoclinic crystal system (space group P2 1 /n). Graphical tool, Hirshfeld surface analysis quantified the major contribution of H⋅⋅⋅H, O⋅⋅⋅H, and C⋅⋅⋅H interactions towards the HS. Among the synthesized compounds, 2-(4-(4-fluorophenyl)-5-(2,8-dimethylH-imidazo[1,2-a]pyridin-3-yl)-4H-1,2,4triazol-3-ylthio)-N-(4-fluorophenyl)acetamide (5 a) exhibited the highest cytotoxicity against lung adenocarcinoma with IC 50 value of 43.04 μM. Selective action of 5 a was assured by cell death analysis using AO-EB assay. In addition, the study was also supported by molecular docking studies. Together the study revealed, the compound 5 a, to be a likely candidate for further exploratory study in cancer treatment.
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