2. Academic Validation
  3. 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

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

  • Bioorg Med Chem. 2021 Aug 1:43:116277. doi: 10.1016/j.bmc.2021.116277.
Dilep Kumar Sigalapalli 1,  Gaddam Kiranmai 2,  G Parimala Devi 3,  Ramya Tokala 1,  Sravani Sana 1,  Chaturvedula Tripura 2,  Govinda Shivaji Jadhav 1,  Manasa Kadagathur 1,  Nagula Shankaraiah 4,  Narayana Nagesh 5,  Bathini Nagendra Babu 6,  Neelima D Tangellamudi 7
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India.
  • 2 CSIR-Centre for Cellular and Molecular Biology, Medical Biotechnology Complex, ANNEXE II, Uppal Road, Hyderabad 500007, India.
  • 3 Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India.
  • 4 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: shankar@niperhyd.ac.in.
  • 5 CSIR-Centre for Cellular and Molecular Biology, Medical Biotechnology Complex, ANNEXE II, Uppal Road, Hyderabad 500007, India. Electronic address: nagesh@ccmb.res.in.
  • 6 Department of Fluoro-Agrochemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India. Electronic address: bathini@iict.res.in.
  • 7 Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500037, India. Electronic address: tdneelima@gmail.com.
PMID: 34175586 DOI: 10.1016/j.bmc.2021.116277
Abstract

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.

Keywords

1,3,4-oxadiazole; ADME/T; Apoptosis; Cytotoxicity; Imidazo[1,2-a]pyridine; Molecular docking; Tubulin polymerization.

Figures