ISSN print edition: 0366-6352 ISSN electronic edition: 1336-9075 Registr. No.: MK SR 9/7 Published monthly

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)