title: Design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives as human dihydroorotate dehydrogenase (hDHODH) inhibitors and anticancer agents.
abstract: In continuation of our research for novel human dihydroorotate dehydrogenase (hDHODH) inhibitors, herein we reported design, synthesis and pharmacological evaluation of novel substituted quinoline-2-carboxamide derivatives. Human DHODH enzyme inhibition assay was used to screen the synthesized compounds as hDHODH inhibitors. The synthesized compounds were also evaluated for their antiproliferative effects on the cancer cell lines (HEP-3B and A-375) to establish a proof as anticancer agents. The chemical structures of compounds were confirmed by (1)H, (13)C NMR, IR, MS and elemental analysis. The purity of compounds was also checked by HPLC analysis. Compounds with bulky groups (-OCH3, -OCF3 and -CF3) at C6-position of quinoline ring showed good activity.
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Vivek K
authors.initials: VK
authors.lastname: Vyas
authors.affiliation: Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India.
authors.forename: Bhavesh
authors.initials: B
authors.lastname: Variya
authors.affiliation: Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382481, Gujarat, India. Electronic address: manjunath.ghate@nirmauni.ac.in.
authors.forename: Manjunath D
authors.initials: MD
authors.lastname: Ghate
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000090722:Dihydroorotate Dehydrogenase; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D000090722:Dihydroorotate Dehydrogenase; D004791:Enzyme Inhibitors; D011804:Quinolines; D044925:Oxidoreductases Acting on CH-CH Group Donors
keywords: Anticancer agents; Dihydroorotate dehydrogenase (DHODH); Pyrimidine biosynthesis; Quinolines; hDHODH inhibitors