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Carbonic anhydrase (CA) II plays major roles in pH regulation of body, protection of electrolyte balance, transportation of water and some metabolic pathways. Therefore, CA II inhibitors are very important molecules for drug design and have many pharmacological applications. CA II as a target molecule is also important for eliminating some pathological conditions such as glaucoma, cancer, epilepsy, ulcer and obesity. In this study, some 1,2,4-triazole derivatives were synthesized and CA II inhibition potentials of these molecules were examined. It has been found that molecule 7c was the most potent inhibitor with the lowest IC50 value at micromolar level among the examined molecules. The inhibition in the range of 18.41–64.97% was seen in the presence of newly synthesized molecules at their reachable maximum concentration in the reaction mixtures. Kinetic studies showed that the inhibition mechanism of compound 7c on carbonic anhydrase activity was reversible and uncompetitive. Molecular docking studies also indicated that compound 7c could bind to the active site of the enzyme by weakly interacting with especially Gln102, Leu240, Ala241 and Trp243. ADME properties of these newly synthesized (3a-e, 6, 7a-e) were also studied and showed good oral drug candidate like properties.

Tyrosinase inhibition is very important in controlling melanin synthesis. If melanin synthesis is not controlled in metabolism, an unwanted increase in melanin synthesis occurs. As melanin plays a role in the formation of skin color, its unusual levels cause some skin disorders such as pregnancy scars, age spots, and especially skin cancer (melanoma). However, the tyrosinase activity is also related to Parkinson-s disease and some neurodegenerative diseases. For all these reasons, the medicinal as well as the cosmetic industries focus on research on tyrosinase inhibitors for the treatment of skin disorders and some neurodegenerative diseases. In this study, 32 new 1,2,4-triazole-(thio)semicarbazide hybrid molecules (6a-p and 7a-p) were synthesized, starting from 4-amino-1-pentyl-3-phenyl-1H-1,2,4-triazole-5(4H)-one. These compounds were evaluated for their inhibitory activity against mushroom tyrosinase. The results indicated that 6h, 6m, 6n, and 6p exhibited the most effective inhibitory activity, with IC50 values of 0.00162 +/- 0.0109, 0.00166 +/- 0.0217, 0.00165 +/- 0.019, and 0.00197 +/- 0.0063 mu M, respectively, compared with kojic acid as the reference drug (IC50 = 14.09 +/- 0.02 mu M). Also, molecular docking analyses were performed to suggest possible binding poses for the ligands. As a result, derivatives 6h, 6m, 6n, and 6p can be used as promising tyrosinase inhibitor candidates in the medicinal, cosmetics, or food industries.