2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of antibacterial and anticancer activities

Mukund P Tantak; Jing Wang; Rajnish Prakash Singh; Anil Kumar; Kavita Shah; Dalip Kumar

doi:10.1016/j.bmcl.2015.07.105

2-(3'-Indolyl)-N-arylthiazole-4-carboxamides: Synthesis and evaluation of antibacterial and anticancer activities

Bioorg Med Chem Lett. 2015 Oct 1;25(19):4225-31. doi: 10.1016/j.bmcl.2015.07.105. Epub 2015 Aug 6.

Authors

Mukund P Tantak¹, Jing Wang², Rajnish Prakash Singh³, Anil Kumar¹, Kavita Shah⁴, Dalip Kumar⁵

Affiliations

¹ Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
² Department of Chemistry, Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
³ Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
⁴ Department of Chemistry, Purdue Cancer Center, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA. Electronic address: shah23@purdue.edu.
⁵ Department of Chemistry, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.

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.

Keywords: Antibacterial; Apoptosis; Cancer; Cytotoxicity; Indoles; Thiazole carboxamides.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Amides / chemical synthesis
Amides / chemistry
Amides / pharmacology*
Anti-Bacterial Agents / chemical synthesis
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology*
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Death / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Gram-Negative Bacteria / drug effects*
Gram-Positive Bacteria / drug effects*
Humans
Indoles / chemical synthesis
Indoles / chemistry
Indoles / pharmacology*
Microbial Sensitivity Tests
Molecular Structure
Structure-Activity Relationship
Thiazoles / chemical synthesis
Thiazoles / chemistry
Thiazoles / pharmacology*

Substances

Amides
Anti-Bacterial Agents
Antineoplastic Agents
Indoles
Thiazoles

Abstract

Publication types

MeSH terms

Substances

Grants and funding