Synthesis and In Vitro Evaluation of Substituted Quinolines as New Apoptosis Inducers and Anticancer Agents: Pharmacophore-based Design

Title:Synthesis and In Vitro Evaluation of Substituted Quinolines as New Apoptosis Inducers and Anticancer Agents: Pharmacophore-based Design

Volume: 18 Issue: 11

Author(s): Hiren Dayani, Abhishek Jha, Manjunath Ghate and Vivek K. Vyas*

Affiliation:

• Department of Pharmaceutical Chemistry, Institute of Pharmacy, Nirma University, Ahmedabad 382 481, Gujarat,India

Keywords: Pharmacophore modeling, Substituted quinolines, Apoptosis inducers, Anticancer agents, Caspase-3 activation assay, annexine-FITC assays.

Abstract:

Background: Cancer is a global health burden and the leading cause of death across the world after cardiovascular disease.

Objective: The objective of this work was the design, synthesis, and pharmacological evaluation of 2-phenylquinolin-4-amine derivatives as apoptosis inducers and anticancer agents.

Methods: In this study, we performed ligand-based pharmacophore modeling as a promising design strategy for the design of substituted quinoline derivatives as apoptosis inducers and anticancer agents. The designed compounds were synthesized as 2-phenylquinolin-4-amine derivatives and characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and Mass spectroscopy. Synthesized compounds were screened for apoptosis-inducing activity using caspase-3 activation and annexine-FITC assays, and also screened against cancer cell line (HT-29) in an antiproliferative assay.

Results: Synthesized compounds 7a, and 7d demonstrated EC₅₀ values of 6.06 and 6.69 μM in caspase-3 activation assay, respectively, and also showed late stage induction of apoptosis in annexine assay. Synthesized compounds 7a, 7d and 7i, also exhibited good antiproliferative activity with IC₅₀ values of 8.12, 9.19, and 11.34 μM, respectively, which revealed that these are promising apoptosis inducers for the further development of new anticancer agents.

Cite this article as:

Dayani Hiren , Jha Abhishek , Ghate Manjunath and Vyas K. Vivek *, Synthesis and In Vitro Evaluation of Substituted Quinolines as New Apoptosis Inducers and Anticancer Agents: Pharmacophore-based Design, Letters in Drug Design & Discovery 2021; 18 (11) . https://dx.doi.org/10.2174/1570180818666210706105347