Synthesis of Thiazole‐Chalcone Hybrid Molecules: Antioxidant, Alpha(α)‐Amylase Inhibition and Docking Studies

Abstract

The molecular hybrid approach is very significant to combat various drug-resistant disorders. A simple, convenient, and cost-effective synthesis of thiazole-based chalcones is accomplished, using a molecular hybrid approach, in two steps. The compound 1-(2-phenylthiazol-4-yl)ethanone (3) was used as the main intermediate for the synthesis of 3-(arylidene)-1-(2-phenylthiazol-4-yl)prop-2-en-1-ones (4a-f). Thin layer chromatography was used to testify the formation and purity of all synthesized compounds. Further structural confirmation of all compounds was achieved via different spectroscopic techniques (UV, FT-IR, 1 H-and 13 C-NMR) and elemental analysis. All synthesized compounds were tested for their α-amylase inhibition and antioxidant potential. The cytotoxic property of compounds was also tested with in vitro haemolytic assay. All tested compounds showed moderate to excellent α-amylase inhibition and antioxidant activity. All tested compounds are found safe to use due to their less toxicity when compared to the standard Triton X. The molecular docking simulation study of all synthesized compounds was also conducted to examine the best binding interactions with human pancreatic αamylase (pdb: 4 W93) using AutodockVina. The molecular docking results authenticated the in vitro amylase inhibition results, i.e., 3-(3-Methoxyphenyl)-1-(2-phenylthiazol-4-yl)prop-2-en-1-one (4e) exhibited lowest IC 50 value 54.09 � 0.11 μM with a binding energy of À 7.898 kcal/mol.

Design, Synthesis, Characterization, Enzyme Inhibition, Molecular Docking, and Pharmacological Evaluation of New Chalcone‐Sulfonate Derivatives Bearing Thiophene

“…Chalcones and their skeletal system widely exist in many natural compounds and are a very attractive tool for the synthesis of different heterocyclic compounds. [1][2][3] Chalcones show various biological activities such as antioxidant, [4,5] antimicrobial, [6,7] antiinfammatory, [8] antihypertensive, [9] antihistaminic, [10] anticancer. [11] Thiophene-based chalcones also show many biological activities such as antibacterial, [12] anticancer (Figure 1, compound 1), [13] and enzyme inhibition (Figure 1, compound 2).…”

Design, Synthesis, and Antifungal Activities of Novel Carboxamides Derivatives Bearing a Chalcone Scaffold as Potential SDHIs

“…[17] Numerous studies have been conducted to explore the structures of chalcones to obtain more drug and pesticide candidates based on molecular hybridization, which is a common and useful strategy. [26][27][28][29] In this work, a series of novel pyrazole-4-carboxamides 5 a-5 l, 8 a, 8 b and 11 containing a chalcone scaffold were designed and synthesized based on molecular hybridization (Figure 2). Subsequently, in vitro antifungal activities of these target compounds against five plant pathogenic fungi (Rhizoctoinia solani; Sclerotinia sclerotiorum; Botrytis cinerea; Fusarium graminearum; and Alternaria alternate.)…”

“…Moreover, some chalcone derivatives such as metochalcone and sofalcone have been clinically approved due to their convenient synthesis, outstanding bioactivities, and low toxicity (Figure 2). [17] Numerous studies have been conducted to explore the structures of chalcones to obtain more drug and pesticide candidates based on molecular hybridization, which is a common and useful strategy [26–29] . In this work, a series of novel pyrazole‐4‐carboxamides 5 a – 5 l , 8 a , 8 b and 11 containing a chalcone scaffold were designed and synthesized based on molecular hybridization (Figure 2).…”