Issue 43, 2024

Synthesis, in vitro biological evaluation and in silico studies of novel pyrrolidine derived thiosemicarbazones as dihydrofolate reductase inhibitors

Abstract

Dihydrofolate reductase (DHFR) is a crucial enzyme involved in folate metabolism and serves as a prime target for anticancer and antimicrobial therapies. In this study, a series of 4-pyrrolidine-based thiosemicarbazones were synthesized and evaluated for their DHFR inhibitory activity. The synthesis involved a multistep procedure starting from readily available starting materials, leading to the formation of diverse thiosemicarbazone 5(a–r) derivatives. These compounds were then subjected to in vitro assays to evaluate their inhibitory potential against DHFR enzyme. The synthesized compounds 5(a–r) exhibited potent inhibition with IC50 values in the range of 12.37 ± 0.48 μM to 54.10 ± 0.72 μM. Among all the derivatives 5d displayed highest inhibitory activity. Furthermore, molecular docking and ADME studies were performed to understand the binding interactions between the synthesized compounds and the active site of DHFR. The in vitro and in silico data were correlated to identify compounds with promising inhibitory activity and favorable binding modes. This comprehensive study provides insights into the structure–activity relationships of 4-pyrrolidine-based thiosemicarbazones as DHFR inhibitors, offering potential candidates for further optimization towards the development of novel therapeutic agents.

Graphical abstract: Synthesis, in vitro biological evaluation and in silico studies of novel pyrrolidine derived thiosemicarbazones as dihydrofolate reductase inhibitors

Supplementary files

Article information

Article type
Paper
Submitted
13 Jul 2024
Accepted
25 Sep 2024
First published
08 Oct 2024
This article is Open Access
Creative Commons BY-NC license

RSC Adv., 2024,14, 31409-31421

Synthesis, in vitro biological evaluation and in silico studies of novel pyrrolidine derived thiosemicarbazones as dihydrofolate reductase inhibitors

H. Aftab, S. Ullah, A. Khan, M. al-Rashida, T. Islam, A. Alshammari, N. A. Albekairi, P. Taslimi, A. Al-Harrasi, Z. Shafiq and S. Alghamdi, RSC Adv., 2024, 14, 31409 DOI: 10.1039/D4RA05071A

This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. You can use material from this article in other publications, without requesting further permission from the RSC, provided that the correct acknowledgement is given and it is not used for commercial purposes.

To request permission to reproduce material from this article in a commercial publication, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party commercial publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements