Synthesis, anti-diabetic profiling and molecular docking studies of 2-(2-arylidenehydrazinyl)thiazol-4(5<i>H</i>)-ones
Creators: name: Mehmood, Hasnain
name: Haroon, Muhammad
name: Akhtar, Tashfeen
name: Woodward, Simon
name: Haq, Saadia
name: Alshehri, Saad M
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Biochemistry
subject: Pharmacology
subject: Biotechnology
subject: Chemical Sciences not elsewhere classified
subject: Ecology
subject: FOS: Biological sciences
subject: Infectious Diseases
subject: FOS: Health sciences

description: <b>Aim:</b> To synthesize novel more potent anti-diabetic agents. <b>Methodology:</b> A simple cost effective <i>Hantzsch's</i> synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5<i>H</i>)-ones. <b>Results:</b> Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5<i>H</i>)-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation and anti-oxidant activities it is revealed that most of the compounds possess good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of α-amylase and anti-oxidant inhibition revealed that compounds are less active against α-amylase and anti-oxidant assays. <b>Conclusion:</b> This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug. Diabetes is a most spreading chronicle disease effecting millions of peoples across the globe every year and this number increases day by day. To cure the human population from this dilemma, we had synthesized, characterized and evaluated the anti-diabetic behavior of our synthesized compounds. α-Amylase, <i>in vitro</i> anti-glycation and anti-oxidant assays were performed to find out good lead for Diabetes Mellitus. All tested compounds were found to be excellent anti-glycating agents with IC<sub>50</sub> values far better than standard amino-guanidine (IC<sub>50</sub> = 3.582 ± 0.002 μM). Compound <b>4m</b> was most efficient glycation inhibitor (IC<sub>50</sub> = 1.095 ± 0.002 μM). Cytotoxicity of all compounds was determined with <i>in vitro</i> hemolytic assay and found all compounds safe and bio-compatible to humans at all tested concentrations. The inhibition potential was also examined with theoretical docking studies to support our experimental results against human pancreatic alpha-amylase (HPA) and human serum albumin (HSA) proteins. All compounds showed excellent binding affinity with HSA active pockets however, only compound <b>4h</b> and <b>4k</b> binding affinity was good with HPA. Thiazol-4-ones are the most effective heterocyclic compounds among other azoles due to large number of biological applications. A large number of commercially available pharmaceutical drugs contain this nucleus. In current study, a simple two-step synthetic protocol was adopted to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5<i>H</i>)-ones. The proposed structures were analyzed and confirmed with routine spectroscopic techniques. Functional groups were justified with FTIR spectroscopic data. Total number of proton and carbons present within the proposed structures were justified with NMR spectroscopic data and confirmation of proposed analogs was ascertain with HRMS. The synthesized analogs were tested for their anti-diabetic potential. Following biological assays were used to determine the anti-diabetic potential of synthesized compounds; α-amylase, anti-glycation and anti-oxidant. From α-amylase assay we concluded that none of the tested compounds is a better α-amylase inhibitor. All tested compounds showed excellent anti-glycation potential. Free radical scavenging assay revealed only compound <b>4h</b> to be an excellent anti-oxidant agent. <i>In vitro</i> hemolytic assay determined almost all compounds are safe to use and found them bio-compatible. Molecular docking study was used to find out the ligand and receptor interactions with AutoDock vina software. From study, it is hypothesized that attachment of electron withdrawing groups and further substitution at the arylidene and thiazole-4-one rings could help to find out the best anti-diabetic scaffold.