Design, synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6 (1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine analogues as antiproliferative agents

Surendar Chitti; SrinivasaRao Singireddi; Pochana Santosh Kumar Reddy; Prakruti Trivedi; Yamini Bobde; Chandan Kumar; Krishnan Rangan; Balaram Ghosh; Kondapalli Venkata Gowri Chandra Sekhar

doi:10.1016/j.bmcl.2019.08.013

Design, synthesis and biological evaluation of 2-(3,4-dimethoxyphenyl)-6 (1,2,3,6-tetrahydropyridin-4-yl)imidazo[1,2-a]pyridine analogues as antiproliferative agents

Bioorg Med Chem Lett. 2019 Sep 15;29(18):2551-2558. doi: 10.1016/j.bmcl.2019.08.013. Epub 2019 Aug 7.

Authors

Surendar Chitti¹, SrinivasaRao Singireddi¹, Pochana Santosh Kumar Reddy¹, Prakruti Trivedi², Yamini Bobde², Chandan Kumar³, Krishnan Rangan¹, Balaram Ghosh⁴, Kondapalli Venkata Gowri Chandra Sekhar⁵

Affiliations

¹ Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India.
² Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India.
³ Department of Bioinformatics, Pondicherry University, Pondicherry 605014, India.
⁴ Department of Pharmacy, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India. Electronic address: balaram@hyderabad.bits-pilani.ac.in.
⁵ Department of Chemistry, Birla Institute of Technology and Science, Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, Telangana, India. Electronic address: kvgc@hyderabad.bits-pilani.ac.in.

PMID: 31420269
DOI: 10.1016/j.bmcl.2019.08.013

Abstract

Two series of forty five novel 2-(3,4-dimethoxyphenyl)-6-(1,2,3,6-tetrahydropyridin-4-yl) imidazo[1,2-a]pyridine analogues (IPA 1-22, IPS 1-22 and IP-NH) have been designed, synthesized and structures confirmed by ¹H NMR, ¹³C NMR, mass spectrometry. Furthermore, single crystal was developed for IPS-13. All the final derived conjugates were evaluated for their in vitro antiproliferative activity against a panel of diverse cancer cell lines viz., A549 (lung cancer), HeLa (cervical cancer), B16F10 (melanoma) and found to show potent anticancer activity on the tested cell lines. Many of them showed the IC₅₀ values in the range 2.0-20.0 µM. The most active compounds (IPA 5,6,8,9,12,16,17,19 and IPS 7,8,9,22) from IPA and IPS series were screened to determine their cytotoxicity on HEK-293 (human embryonic kidney) normal cell line and were found to be nontoxic to normal human cells. The molecular interactions of the derivatised conjugates were also supported by molecular docking simulations. These derivatives may serve as lead structures for development of novel potential anticancer drug candidates.

Keywords: Anticancer; Apoptosis; Cytotoxicity; Imidazo[1,2-a]pyridine; Molecular docking.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

A549 Cells
Animals
Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Design*
Drug Screening Assays, Antitumor
HeLa Cells
Humans
Mice
Molecular Structure
Pyridines / chemical synthesis
Pyridines / chemistry
Pyridines / pharmacology*
Structure-Activity Relationship

Substances

Antineoplastic Agents
Pyridines
imidazo(1,2-a)pyridine