title: Design, synthesis and molecular modeling of pyrazole-quinoline-pyridine hybrids as a new class of antimicrobial and anticancer agents.
abstract: A new series of pyrazole-quinoline-pyridine hybrids were designed based on molecular hybridization technique and synthesized by a base-catalyzed cyclocondensation reaction through one-pot multicomponent reaction. All compounds were tested for in vitro antibacterial and anticancer activities. Enzyme inhibitory activities of all compounds were carried out against FabH and EGFR. Of the compounds studied, majority of the compounds showed effective antibacterial as well as anticancer activity against used strains and cancer cell lines respectively. Compound 7k (IC₅₀ = 0.51 ± 0.05 μM) against EGFR and 7b displayed the most potent inhibitory activity with IC₅₀ of 3.1 μM against FabH as compared to other member of the series. In the molecular modeling study, compound 7k was bound in to the active pocket of EGFR with three hydrogen bond and one π-cation interaction with minimum binding energy ΔGb = -54.6913 kcal/mol, as well as compound 7b was bound in to the active site of FabH with hydrogen bond and π-sigma interactions with minimum binding energy ΔGb = -45.9125 kcal/mol.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Chetan B
authors.initials: CB
authors.lastname: Sangani
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Jigar A
authors.initials: JA
authors.lastname: Makawana
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Shashikant B
authors.initials: SB
authors.lastname: Teraiya
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, China. Electronic address: zhuhl@nju.edu.cn.
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D020128:Inhibitory Concentration 50; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D011720:Pyrazoles; D011725:Pyridines; D011804:Quinolines; D066246:ErbB Receptors
keywords: 1H-Pyrazole-4-carbaldehyde; 4H-Quinoline; Antibacterial activity; Anticancer activity; Molecular modeling; One-pot reaction; Pyridine