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Design and Synthesis of Piperazine‐Linked Imidazo[1,2‐ a ]pyridine Derivatives as Potent Anticancer Agents
Author(s) -
Reddy Gangireddy Madhusudhana,
Mantipally Manohar,
Gundla Rambabu,
Nayak Badavath Vishnu,
Paidikondala Kalyani,
Yamala Anilkumar
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201902955
Subject(s) - piperazine , chemistry , hela , stereochemistry , pyridine , cytotoxicity , trifluoromethyl , pyrimidine , in vitro , medicinal chemistry , biochemistry , organic chemistry , alkyl
Designed, synthesized a series of novel imidazo[1,2‐ a ]pyridine derivatives and evaluated for their in vitro cytotoxicity. Fluorine containing compounds, (2‐fluorophenyl)(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐ a ]pyridin‐6‐yl)piperazin‐1‐yl)methanone ( 7 e) ,(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐ a ]pyridin‐6‐yl)piperazin‐1‐yl)(2‐(trifluoromethyl)phenyl)methanone (7 h) and (3‐fluorophenyl)(4‐(2‐(pyridin‐2‐yl)imidazo[1,2‐ a ]pyridin‐6‐yl)piperazin‐1‐yl)methanone ( 7 i ) were found to have an effective cytotoxic profile against HepG2, HeLa and MDA‐MB‐231. Compounds 7 h (IC 50 = 5.8 μM) and 7 i (IC 50 = 3.5 μM) were found potent when compared with control Paclitaxel (IC 50 = 2.8 μM), against HeLa. Compound 7 h also found to be potent against HepG2 (IC 50 = 2.0 μM) and MDAMB‐231(IC 50 = 6.9 μM) respectively, when compared with Paclitaxel (HepG2, IC 50 = 0.56 μM; MDAMB‐231, IC 50 = 1.9 μM). Compound 7 e also found to be potent against HepG2 (IC 50 = 9.8 μM) cell lines. Synthesized piperazine linked imidazo[1,2‐ a ]pyridine derivatives ( 7 i , IC 50 =3.5 μM) and ( 7 h , IC 50 =5.8 μM) showed 1.74 fold, 1.12 fold increase in antiproliferative activity than reported homopiperazine linked imidazo[1,2‐ a ]pyrimidine derivatives (4‐Fluorophenyl)(4‐(2‐(4‐fluorophenyl)imidazo[1,2‐ a ]pyrimidin‐7‐yl)‐1,4‐diazepan‐1‐yl)methanone( 10 f , IC 50 =6.12 μM) and (4‐(2‐(4‐Fluorophenyl)imidazo[1,2‐ a ]pyrimidin‐7‐yl)‐1,4‐diazepan‐1‐yl)(3‐methoxyphenyl)methanone ( 12 , IC 50 =6.54 μM) against Hela cell lines. Molecular docking studies showed that designed compounds occupy at the active site of both colchicine and human estrogen receptor which demonstrated that the designed compounds were able to bind with multiple targets, the biological activity of these compounds hold promise to find application in considering for treatment protocol.