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ISSN print edition: 0366-6352
ISSN electronic edition: 1336-9075
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Synthesis of small size adamantane-linked aminothiazoles as potent inhibitors of urease, α-glucosidase and carbonic anhydrase and their molecular docking studies
Atteeque Ahmed, Pervaiz Ali Channar, Syeda Abida Ejaz, Aamer Saeed, Muhammad Saleem, Tahira Shamim, Tanveer A. Wani, Jabir Hussain, Nadeem Gul, Siraj Khan, Seema Zargar, and Chen Li
Department of Chemistry, Quaid-I-Azam University Islamabad, Islamabad, Pakistan
E-mail: aahmed@chem.qau.edu.pk
Received: 14 February 2024 Accepted: 16 June 2024
Abstract:
The current study was aimed to synthesize a series of adamantane-linked aminothiazole derivatives (6a-) and to assess their enzyme inhibitory activities. These derivatives were synthesized based on the structural features of known enzyme inhibitors, and their structures were characterized using various spectroscopic techniques, including FTIR, 1H NMR, 13C NMR, and mass spectrometry. The synthesized compounds were further evaluated for their inhibitory activities against the enzymes urease, α-glucosidase and carbonic anhydrase. The results of the enzyme inhibitory activity showed that compounds 6c, 6g and 6k possessed an excellent urease inhibitory activities, with IC50 values of 18.07 ± 0.11, 13.05 ± 0.2 and 17.12 ± 0.1 µM, respectively. These values were significantly lower than the IC50 value of the standard inhibitor thiourea (21,021 ± 0.02 µM). Additionally, compound 6c and 6e showed good α-glucosidase inhibitory activities. Therefore, compound 6c and 6e has excellent activity of IC50 value as 18.4 ± 0.11 and 58.01 ± 0.8 µM against α-glucosidase enzyme, respectively, and considerable relative potency compared with the known α-glucosidase inhibitor i.e., acarbose having an IC50 value of 883.93 ± 2.18 µM. The inhibitory effect of the compound 6f, 6k, 6j was considerably high against carbonic anhydrase, with their IC50 values of 3.02 ± 0.31 µM, 4.5 ± 0.041 µM and 2.7 ± 0.004 µM, respectively, as compared to acetazolamide with an IC50 value of IC50 0.12 ± 0.03 µM. The molecular docking of the active compounds docked in the active site of urease, α-glucosidase enzyme and carbonic anhydrase and depicted a good-binding score for all active derivatives. The present results indicate the significance of the structure–activity relationship in the development of potent enzyme inhibitors. Hence, the results obtained from the current study may be useful for designing further studies on related compounds with potential medicinal importance.
Graphical abstract
Keywords: Adamantane; Aminothiazole; α-Glucosidase; Urease; Thiourea; Acarbose
Full paper is available at www.springerlink.com.
DOI: 10.1007/s11696-024-03572-6
Chemical Papers 78 (11) 6747–6770 (2024)