Synthesis and biological evaluation of novel imidazo[1,2-a]pyridine-oxadiazole hybrids as anti-proliferative agents: Study of microtubule polymerization inhibition and DNA binding

• Published in: Bioorganic & medicinal chemistry Vol. 43; p. 116277
• Main Authors: Sigalapalli, Dilep Kumar, Kiranmai, Gaddam, Parimala Devi, G., Tokala, Ramya, Sana, Sravani, Tripura, Chaturvedula, Jadhav, Govinda Shivaji, Kadagathur, Manasa, Shankaraiah, Nagula, Nagesh, Narayana, Babu, Bathini Nagendra, Tangellamudi, Neelima D.
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2021
• Subjects: 1,3,4-oxadiazole; ADME/T; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis; Binding Sites; Cell Line; Cell Proliferation - drug effects; Cytotoxicity; DNA - chemistry; Dose-Response Relationship, Drug; Drug Design; Drug Screening Assays, Antitumor; Humans; Imidazo[1,2-a]pyridine; Microtubules - drug effects; Microtubules - metabolism; Molecular docking; Molecular Structure; Oxadiazoles - chemistry; Oxadiazoles - pharmacology; Polymerization - drug effects; Pyridines - chemistry; Pyridines - pharmacology; Structure-Activity Relationship; Tubulin polymerization; 1,3,4-oxadiazole; Cytotoxicity; ADME/T; Molecular docking; Imidazo[1,2-a]pyridine; Apoptosis; Tubulin polymerization
• ISSN: 0968-0896; 1464-3391
• DOI: 10.1016/j.bmc.2021.116277

[Display omitted] •Compound6d displayed significant cytotoxicity and magnificent cytospecificity towards the cancer cell lines.•Compound6d induced apoptosis in A549 lung cancer cell line.•Compound6d significantlyinhibited tubulin polymerization and shows effective binding with CT-DNA.•Molecular modelling studies established the binding of 6d with α/β-tubulin. Efforts towards the development of potential anticancer agents, a new series of imidazo[1,2-a]pyridine-oxadiazole hybrids were synthesized and evaluated for their in vitro anticancer activity against lung cancer (A549) and prostate cancer (PC-3, DU-145) cell lines. Amongst the compounds tested, 6d showed the highest potency on A549 cells with an IC50 value of 2.8 ± 0.02 μM. Flow cytometric analysis of compound 6d treated A549 cells showed apoptosis induction by annexin-v/PI dual staining assay and the effect of 6d on different phases of cell cycle was also analyzed. Target based studies demonstrated the inhibition of tubulin polymerization by 6d at an IC50 value of 3.45 ± 0.51 μM and its effective binding with CT-DNA. Further, the molecular modelling studies revealed that 6d has a prominent binding affinity towards α/β-tubulin receptor with admirable physico-chemical properties.