Issue 15, 2023

Novel asymmetrical azines appending 1,3,4-thiadiazole sulfonamide: synthesis, molecular structure analyses, in silico ADME, and cytotoxic effect

Abstract

Toward finding potential and novel anticancer agents, we designed and prepared novel differently substituted unsymmetrical azine-modified thiadiazole sulfonamide derivatives using the “combi-targeting approach”. An efficient procedure for synthesizing the designed compounds starts with 5-acetyl-3-N-(4-sulfamoylphenyl)-2-imino-1,3,4-thiadi-azoline 4. The E/Z configuration for compound 5 was investigated based on spectral analysis combined with quantum mechanical calculation applying the DFT-B3LYP method and 6-31G(d) basis set. The computational results found that the E isomer was energetically more favorable than the Z isomer by 2.21 kcal mol−1. Moreover, 1H and 13C chemical shifts for the E and Z isomers in DMSO were predicted using the GIAO-B3LYP/6-31G(d) computations and IEF-PCM solvation model. The computed chemical shifts for both isomers are consistent with those observed experimentally, indicating that they exist in the solution phase. Moreover, the E/Z configuration for the synthesized azines 7a–c, 9, 11, 13, 15a and 15b was also studied theoretically using the DFT-B3LYP/6-31G(d) calculations. In silico prediction for the biological activities was reported regarding the HOMO–LUMO energy gaps and molecular reactivity descriptors besides the ADMT/drug-likeness properties. The cytotoxic effect of the synthesized compounds has been assayed via the determination of their IC50.

Graphical abstract: Novel asymmetrical azines appending 1,3,4-thiadiazole sulfonamide: synthesis, molecular structure analyses, in silico ADME, and cytotoxic effect

Supplementary files

Article information

Article type
Paper
Submitted
07 jan. 2023
Accepted
21 mar. 2023
First published
03 apr. 2023
This article is Open Access
Creative Commons BY license

RSC Adv., 2023,13, 10353-10366

Novel asymmetrical azines appending 1,3,4-thiadiazole sulfonamide: synthesis, molecular structure analyses, in silico ADME, and cytotoxic effect

S. Bondock, T. Albarqi, I. A. Shaaban and M. M. Abdou, RSC Adv., 2023, 13, 10353 DOI: 10.1039/D3RA00123G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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