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Candida species have long been attributed to various diseases like candidiasis and systemic diseases and exacerbate the symptoms of immunocompromised patients. Candida species have enzymes that could function as drug targets to decrease their pathogenicity and eradicate the fungi. This research aimed to investigate the potency of new bis-triazolothiadiazine derivatives contained in inhibiting important enzymes of C. albicans as an example, through molecular docking simulation. Thus, a novel series of bis-triazolo[3,4-b][1,3,4]thiadiazines were designed and prepared via the reaction of the most versatile, hitherto unreported 5,5′-(1,2,2-trimethylcyclopentane-1,3-diyl)bis(4-amino-2,4-dihydro-3H-1,2,4-triazole-3-thione) with the appropriate hydrazonoyl halides and phenacyl bromides. Various spectroscopic techniques were used to identify the structures of the synthesized derivatives. The synthesized derivatives were tested against different species of Candida spp. The most effective compound was 6f followed by 6b, 6d, and 6e, where the inhibition zone ranged from 45 mm to 38 mm. By using molecular docking, which highlighted the important interactions with the amino acid residues Lys57, Leu77, Glu116, Gly114, Phe36, Thr58, and Glu32 at the point of binding, it was possible to determine the binding interactions of the produced derivatives to the fluconazole target fungi. The binding interaction energy was discovered to be −6.494 kcal/mol for the fungi candida albicans (PDB ID: 1IA2). The derivatives 6f and 6d, which demonstrated the highest efficacy, displayed significant conserved interactions with the amino acid residues at the binding site of the fluconazole fungi, in conjunction with the PDB co-crystal ligand 1IA2. The study’s results also revealed that the dG scores of the novel bis-triazolo-thiadiazines 6b-f. The study shows good docking scores with acceptable binding interactions. Finally, molecular docking studies revealed the lowest binding activity of derivatives 6e and 6c with the target fungi. |
