Synthesis, Structure‐Activity Relationship and in silico Studies of Novel Pyrazolothiazole and Thiazolopyridine Derivatives as Prospective Antimicrobial and Anticancer Agents

Abstract

In our attempt to develop potential new drug candidates with promising dual antimicrobial and anticancer activities, a series of pyrazolothiazole and thiazolopyridine analogues has been synthesized. All compounds were evaluated for their antimicrobial potential towards pathogenic strains and cytotoxicity properties against hepatic cancer cell line HepG-2 and breast cancer cell line MCF-7. 9 c showed excellent antimicrobial activity against the tested strains, with MIC values about 27.5 μM (S. epidermidis), 6.8 (B. subtilis) and 3.4 μM (S. pneumoniae and K. pneumoniae) fold higher than the reference drug, whilst 9 a, 9 b and 5 a exhibited also potent activity against selected strains. Moreover, compounds 9 c (IC50 = 10.89 μM and 15.60 μM) and 9 a (IC50 = 22.24 μM and 28.47 μM) showed promising anticancer activity for HepG2 and MCF-7 cell lines, respectively, when compared to the known anticancer drugs, 5-Fluorouracil (IC50 = 26.75 μM and IC50 = 32.75 μM). The data from structure-activity relationships analysis revealed the potency of pyrazolothiazole than thiazolopyridine derivatives in generating potential activity. Further, molecular docking studies performed on the more active antimicrobial and cytotoxic compound, 9 c to get insights for binding modes to the target enzymes (PDB ID: 1JIJ) for antimicrobial, and (PDB ID: 1DI8) and (PDB ID: 3TWJ) for anticancer revealed that they interacted with the same key amino acids with TyrRS for S. aureus, CDK2 and ROCK1, respectively.

Phytochemical Composition, Antioxidant, and Anticancer Activities of Sidr Honey: In Vitro and In Silico Computational Investigation

“…The free-binding energy ranged between −4.3 and −8.7 kcal/mol. Variation in such score values was reported to be related to the 3D chemical structures of the ligands [ 30 , 34 , 66 ]. The best binding score was predicted in the 1di8- Miraxanthin- III (compound eight) complex.…”

Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties of Acacia Honey from the Hail Region: The in vitro and in silico Investigation

“…Furthermore, the binding affinities and molecular interactions of the constituents of honey were assessed against several receptors involved in the studied biological activities (Figure S1). One of these receptors is 1JIJ, which is a S. aureus tyrosyl-tRNA synthetase and is commonly recognized to provide a structural basis for designing novel antimicrobial agents [ 66 , 67 ]. Another one is 2 × ct, which is a type IIA topoisomerase that cleaves and then ligates DNA strands to regulate the DNA topology.…”

“…It was at a distance of only 2.020 Å from Arg1753, which satisfactorily explained the potential biological activity. Furthermore, the molecular interactions of the different complexes usually included certain key residues associated with the pharmacological effects [ 67 , 74 , 75 ]. Overall, the biological effects of the phytochemical compounds in honey appeared to be thermodynamically feasible, particularly those of the tripeptides and aminocyclitol glycoside.…”

Fused Pyridine Derivatives: Synthesis and Biological Activities

“…Antibacterial (against both gram-positive and gram-negative bacteria), antiviral, antifungal, antituberculose, and antiparasitic activity of compounds containing thiazolopyridine structure were reported [247][248][249][250][251]. Additionally, cytotoxic and anticancer activity of thiazolopyridine derivatives were investigated in many studies [252][253][254][255].…”