title: Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of novel quinoline bearing dihydropyridines.
abstract: A new series of eight quinoline bearing dihydropyridine derivatives (A1-A8) were synthesized in high yield and in short reaction time by a four component reaction of 2-chloro-3-fomyl quinoline, malononitrile, arylamines and dimethyl acetylenedicarboxylate in the presence of a catalytic amount of triethylamine. The compounds were fully characterized by IR, NMR and GC-MS. These compounds were screened for potential biological activity in an A549 lung cancer cell line and were also evaluated for their antibacterial activities against Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213 whilst their molecular docking properties in an enzymatic system were also determined. Compounds A2, A3, A4 and A8 showed anti-proliferative activity; with A4 having the highest toxicity at 250μg/mL and A8 has high toxicity at 125, 250 and 500μg/mL, respectively. Antibacterial results indicated that A4 have significant activity against tested microorganisms at the minimum inhibitory concentration (MIC) values of 32μg/mL against Pseudomonas aeruginosa and Escherichia coli, and 16μg/mL against Staphylococcus aureus. Docking of A1 with human mdm2 indicated the lowest binding energy (-6.111Kcal/mol) thereby showing strong affinity of the ligand molecule with the receptor which has been stabilized by strong hydrogen bond interactions in the binding pocket. This confirms that A1 is a better inhibitor for E3 ubiquitin-protein ligase mdm2.
authors.affiliation: Department of Chemistry, Faculty of Applied Science, Durban University of Technology, Durban 4001, South Africa.
authors.forename: S'busiso Mfan'vele
authors.initials: SM
authors.lastname: Nkosi
authors.affiliation: Department of Chemistry, Faculty of Applied Science, Durban University of Technology, Durban 4001, South Africa.
authors.forename: Krishnan
authors.initials: K
authors.lastname: Anand
authors.affiliation: Department of Biotechnology, Bhupath and Jothi Mehtha School of Bioscience, Indian Institute of Technology-Madras, Chennai - 600 036, Tamil Nadu, India.
authors.forename: S
authors.initials: S
authors.lastname: Anandakumar
authors.affiliation: Department of Biomedical Resource Centre, University of KwaZulu-Natal, Westville, Durban 4001, South Africa.
authors.forename: Sanil
authors.initials: S
authors.lastname: Singh
authors.affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine and Medical Sciences, University of KwaZulu-Natal, Durban 4001, South Africa.
authors.forename: Anil Amichund
authors.initials: AA
authors.lastname: Chuturgoon
authors.affiliation: Department of Chemistry, Faculty of Applied Science, Durban University of Technology, Durban 4001, South Africa. Electronic address: genganrm@dut.ac.za.
authors.forename: Robert Moonsamy
authors.initials: RM
authors.lastname: Gengan
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D004095:Dihydropyridines / Q000737:chemistry*; D015195:Drug Design; D062105:Molecular Docking Simulation; D011804:Quinolines / Q000737:chemistry*
chemical_list: D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D004095:Dihydropyridines; D011804:Quinolines; C038806:1,4-dihydropyridine
keywords: 2-Chloro-3-formylquinoline; Anti-cancer; Dihydropyridines; Human mdm2; Molecular docking