title: 2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of antibacterial and anticancer activities.
abstract: A new series of 2-(3'-indolyl)-N-arylthiazole-4-carboxamides 17a-p has been designed and synthesized. Initial reaction of readily available thioamides 15 with bromopyruvic acid under refluxing conditions produced different thiazole carboxylic acids 16 which upon coupling with arylamines by using EDCI·HCl and HOBt afforded diverse arylthiazole-4-carboxamides 17a-p in 78-87% yields. Antibacterial activity evaluation against Gram-positive and Gram-negative bacterial strains led to compounds 17i-k and 17o as potent and selectively (Gram-negative) antibacterial agents. The cytotoxicity of thiazole carboxamides 17a-p was also evaluated on a panel of human cancer cell lines. Among the tested derivatives, compounds 17i (IC50=8.64μM; HEK293T) and 17l (IC50=3.41μM; HeLa) were identified as the most potent analogues of the series. Preliminary mechanism of action studies of thiazole carboxamide 17i suggested that its cytotoxicity against HeLa cells involves the induction of cell death by apoptosis.
authors: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors: Mukund P
authors: MP
authors: Tantak
authors: Department of Chemistry, Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
authors: Jing
authors: J
authors: Wang
authors: Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors: Rajnish Prakash
authors: RP
authors: Singh
authors: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors: Anil
authors: A
authors: Kumar
authors: Department of Chemistry, Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA. Electronic address: shah23@purdue.edu.
authors: Kavita
authors: K
authors: Shah
authors: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.
authors: Dalip
authors: D
authors: Kumar
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000577:Amides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007211:Indoles; D013844:Thiazoles
keywords: Antibacterial; Apoptosis; Cancer; Cytotoxicity; Indoles; Thiazole carboxamides