Bacterial Tyrosinase Inhibition, Hemolytic and Thrombolytic Screening, and In Silico Modeling of Rationally Designed Tosyl Piperazine-Engrafted Dithiocarbamate Derivatives

Abstract

Piperazine is a privileged moiety that is a structural part of many clinical drugs. Piperazine-based scaffolds have attracted the attention of pharmaceutical and medicinal scientists to develop novel, efficient therapeutic agents owing to their significant and promising biological profile. In the current study, an ecofriendly ultrasonic-assisted synthetic approach was applied to achieve a novel series of 1-tosyl piperazine dithiocarbamate acetamide hybrids 4a–4j, which was evaluated for in vitro tyrosinase inhibition and thrombolytic and hemolytic cytotoxic activities. Among all the piperazine-based dithiocarbamate acetamide target molecules 4a–4j, the structural analogs 4d displayed excellent tyrosinase inhibition efficacy (IC50 = 6.88 ± 0.11 µM) which was better than the reference standard drugs kojic acid (30.34 ± 0.75 µM) and ascorbic acid (11.5 ± 1.00 µM), respectively, which was further confirmed by in silico induced-fit docking (IFD) simulation Good tyrosinase activities were exhibited by 4g (IC50 = 7.24 ± 0.15 µM), 4b (IC50 = 8.01 ± 0.11 µM) and 4c (IC50 = 8.1 ± 0.30 µM) dithiocarbamate acetamides, which were also better tyrosinase inhibitors than the reference drugs but were less active than the 4d structural hybrid. All the derivatives are less toxic, having values in the 0.29 ± 0.01% to 15.6 ± 0.5% range. The scaffold 4b demonstrated better hemolytic potential (0.29 ± 0.01%), while a remarkably high thrombolytic chemotherapeutic potential was displayed by analog 4e (67.3 ± 0.2%).

Synthesis, in silico ADMET prediction analysis, and pharmacological evaluation of sulfonamide derivatives tethered with pyrazole or pyridine as anti-diabetic and anti-Alzheimer's agents

“… The biological effects of pyrazole, pyridine, and sulfonamide derivatives. Nitrogenous compounds with multiple biological activities, such as antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic agents ( Zahoor et al, 2023 , Hammouda et al, 2023 , Zhang et al, 2024 , Abdel-Aziz et al, 2015 , Hashem et al, 2023 ). In addition to our previous studies that highlight the development of various compounds and evaluation of their biological effects as potential drug candidates ( Mukhtar et al, 2021 , Hassan et al, 2015 , Morsy et al, 2021 ).…”

“…Nitrogenous compounds with multiple biological activities, such as antioxidant, anti-diabetic, anti-Alzheimer, and anti-arthritic agents ( Zahoor et al, 2023 , Hammouda et al, 2023 , Zhang et al, 2024 , Abdel-Aziz et al, 2015 , Hashem et al, 2023 ).…”

Discovery of novel 1,2,4-triazole tethered β-hydroxy sulfides as bacterial tyrosinase inhibitors: synthesis and biophysical evaluation through in vitro and in silico approaches

“…[20][21][22] Previous research has identied various heterocyclic compounds such as benzofuran-oxadiazole as bacterial tyrosinase inhibitors, 23 oxadiazoles as human tyrosinase inhibitors, 24 and piperazines as bacterial tyrosinase inhibitors. 25 Nitrogenous triazole scaffolds have been found to exhibit mushroom tyrosinase inhibition, such as 1,2,4-triazole hydrazones and 1,2,4-triazole clubbed N-phenylacetamides (Fig. 1).…”