Rational modification of the lead molecule: Enhancement in the anticancer and dihydrofolate reductase inhibitory activity

Jagroop Kaur; Sukhmeet Kaur; Palwinder Singh

doi:10.1016/j.bmcl.2016.03.015

Rational modification of the lead molecule: Enhancement in the anticancer and dihydrofolate reductase inhibitory activity

Bioorg Med Chem Lett. 2016 Apr 15;26(8):1936-40. doi: 10.1016/j.bmcl.2016.03.015. Epub 2016 Mar 7.

Authors

Jagroop Kaur¹, Sukhmeet Kaur¹, Palwinder Singh²

Affiliations

¹ Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India.
² Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India. Electronic address: palwinder_singh_2000@yahoo.com.

PMID: 26979156
DOI: 10.1016/j.bmcl.2016.03.015

Abstract

By using molecular docking studies, the practice of fragment based drug discovery is conceptualized by introducing oxindole and iso-propanol moieties in our previous lead molecule 1. The resulting compound 2 exhibited competitive inhibition and favorable Ka and Ki for hDHFR. The screening of compound 2 at 60 cell line panel of human tumor cell lines showed its considerably better efficacy than compound 1 and hence put the candidature of 2 on stronghold for further studies.

Keywords: Anti-cancer activity; Dihydrofolate reductase; Indole.

Publication types

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

MeSH terms

Antineoplastic Agents / chemical synthesis
Antineoplastic Agents / chemistry*
Antineoplastic Agents / pharmacology*
Cell Line, Tumor
Cell Proliferation / drug effects
Dose-Response Relationship, Drug
Drug Screening Assays, Antitumor
Folic Acid Antagonists / chemical synthesis
Folic Acid Antagonists / chemistry*
Folic Acid Antagonists / pharmacology*
Humans
Molecular Docking Simulation
Molecular Structure
Structure-Activity Relationship
Tetrahydrofolate Dehydrogenase / metabolism*

Substances

Antineoplastic Agents
Folic Acid Antagonists
Tetrahydrofolate Dehydrogenase