QSAR modelling and docking analysis of some thiazole analogues as alfa-glucosidase inhibitors

Muhammad Tukur Ibrahim; Adamu Uzairu; Gideon Adamu Shallangwa; Sani Uba

doi:10.18540/jcecvl5iss3pp0257-0270

Authors

Muhammad Tukur Ibrahim Ahmadu Bello University
Adamu Uzairu Ahmadu Bello University, Zaria
Gideon Adamu Shallangwa Ahmadu Bello University, Zaria
Sani Uba Ahmadu Bello University, Zaria

DOI:

https://doi.org/10.18540/jcecvl5iss3pp0257-0270

Keywords:

QSAR, Molecular modelling, docking, Diabetes

Abstract

QSAR modelling and docking studies on 45 thiazole analogues were carried out. The studied compounds in this research were optimized adopting DFT method at B3LYP function with a 6-31G* basis set. The QSAR models were generated in material studio by MLR analysis (GFA method). Based on its statistical fitness, the first model was selected and chosen as the studied model and assessed with R² = 0.906134, R²_adj = 0.89049, Q²_cv = 0.86149 and R² _pred = 0.82581. The ligand with the highest binding energy of -11.0 kcal/mol among the other ligands was ligand 13 as indicated by the molecular docking. The standard drug (acarbose) was also docked to the binding pocket of alfa-glucosidase with -9.5kcal/mole docking score. The most active compound was found to be better than standard drug. The outcome of this findings paved way for predicting novel ?-glucosidase inhibitors having improved potency toward the target enzyme.

Downloads

Download data is not yet available.

References

Abdulfatai, U., Uzairu, A., and Uba, S. (2017). Quantitative structure-activity relationship and molecular docking studies of a series of quinazolinonyl analogues as inhibitors of gamma amino butyric acid aminotransferase. Journal of advanced research, 8(1), 33-43.

Adedirin, O., Uzairu, A., Shallangwa, G. A., and Abechi, S. E. (2018). QSAR AND MOLECULAR DOCKING BASED DESIGN OF SOME N-BENZYLACETAMIDE AS Γ-AMINOBUTYRATE-AMINOTRANSFERASE INHIBITORS. The Journal of Engineering and Exact Sciences, 4(1), 0065-0084.

Adeniji, S. E., Uba, S., and Uzairu, A. (2018). Quantitative structure-activity relationship and molecular docking of 4-Alkoxy-Cinnamic analogues as anti-mycobacterium tuberculosis. Journal of King Saud University-Science.

Alisi, I. O., Uzairu, A., Abechi, S. E., and Idris, S. O. (2018). Quantitative Structure Activity Relationship Analysis of Coumarins as Free Radical Scavengers by Genetic Function Algorithm. Physical Chemistry Research, 6(1), 209-223.

Amin, S. A., and Gayen, S. (2016). Modelling the cytotoxic activity of pyrazolo-triazole hybrids using descriptors calculated from the open source tool “PaDEL-descriptor”. Journal of Taibah University for Science, 10(6), 896-905.

Arthur, D. E., Uzairu, A., Mamza, P., Abechi, S. E., and Shallangwa, G. (2016). Insilco study on the toxicity of anti-cancer compounds tested against MOLT-4 and p388 cell lines using GA-MLR technique. Beni-Suef University Journal of Basic and Applied Sciences, 5(4), 320-333.

Bibi, S., and Sakata, K. (2016). Current status of computer-aided drug design for type 2 diabetes. Current computer-aided drug design, 12(2), 167-177.

Cheng, L. P., Huang, X. Y., Wang, Z., Kai, Z. P., and Wu, F. H. (2014). Combined 3D-QSAR, molecular docking, and molecular dynamics study on potent cyclohexene-based influenza neuraminidase inhibitors. Monatshefte für Chemie-Chemical Monthly, 145(7), 1213-1225.

Datar, P., and Deokule, T. (2014). Design and synthesis of thiadiazole derivatives as antidiabetic agents. Med chem, 4(4), 390-399.

de Souza, M. V. N. (2005). Synthesis and biological activity of natural thiazoles: An important class of heterocyclic compounds. Journal of Sulfur Chemistry, 26(4-5), 429-449.

Ibrahim, M. T., Uzairu, A., Shallangwa, G. A., and Ibrahim, A. (2018). In-silico studies of some oxadiazoles derivatives as anti-diabetic compounds. Journal of King Saud University-Science.

Kavitha, S., Kannan, K., and Gnanavel, S. (2017). Synthesis, characterization and biological evaluation of novel 2, 5 substituted-1, 3, 4 oxadiazole derivatives. Saudi Pharmaceutical Journal, 25(3), 337-345.

Kenchappa, R., Bodke, Y. D., Chandrashekar, A., Sindhe, M. A., and Peethambar, S. (2017). Synthesis of coumarin derivatives containing pyrazole and indenone rings as potent antioxidant and antihyperglycemic agents. Arabian Journal of Chemistry, 10, S3895-S3906.

Khan, K. M., Qurban, S., Salar, U., Taha, M., Hussain, S., Perveen, S., Hameed, A., Ismail, N. H., Riaz, M., and Wadood, A. (2016). Synthesis, in vitro α-glucosidase inhibitory activity and molecular docking studies of new thiazole derivatives. Bioorganic chemistry, 68, 245-258.

Khan, K. M., Rahim, F., Wadood, A., Kosar, N., Taha, M., Lalani, S., Khan, A., Fakhri, M. I., Junaid, M., and Rehman, W. (2014). Synthesis and molecular docking studies of potent α-glucosidase inhibitors based on biscoumarin skeleton. European journal of medicinal chemistry, 81, 245-252.

Li, W., Zheng, H., Bukuru, J., and De Kimpe, N. (2004). Natural medicines used in the traditional Chinese medical system for therapy of diabetes mellitus. Journal of ethnopharmacology, 92(1), 1-21.

Rahim, F., Ullah, H., Javid, M. T., Wadood, A., Taha, M., Ashraf, M., Shaukat, A., Junaid, M., Hussain, S., and Rehman, W. (2015). Synthesis, in vitro evaluation and molecular docking studies of thiazole derivatives as new inhibitors of α-glucosidase. Bioorganic chemistry, 62, 15-21.

Taha, M., Ismail, N. H., Imran, S., Selvaraj, M., and Rahim, F. (2016). Synthesis of novel inhibitors of β-glucuronidase based on the benzothiazole skeleton and their molecular docking studies. RSC Advances, 6(4), 3003-3012.

Taha, M., Ismail, N. H., Imran, S., Wadood, A., Rahim, F., Saad, S. M., Khan, K. M., and Nasir, A. (2016). Synthesis, molecular docking and α-glucosidase inhibition of 5-aryl-2-(6′-nitrobenzofuran-2′-yl)-1, 3, 4-oxadiazoles. Bioorganic chemistry, 66, 117-123.

Taha, M., Ismail, N. H., Lalani, S., Fatmi, M. Q., Siddiqui, S., Khan, K. M., Imran, S., and Choudhary, M. I. (2015). Synthesis of novel inhibitors of α-glucosidase based on the benzothiazole skeleton containing benzohydrazide moiety and their molecular docking studies. European journal of medicinal chemistry, 92, 387-400.

Tropsha, A., Gramatica, P., and Gombar, V. K. (2003). The importance of being earnest: validation is the absolute essential for successful application and interpretation of QSPR models. Molecular Informatics, 22(1), 69-77.

Trott, O., and Olson, A. J. (2010). AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. Journal of computational chemistry, 31(2), 455-461.

Veerasamy, R., Rajak, H., Jain, A., Sivadasan, S., Varghese, C. P., and Agrawal, R. K. (2011). Validation of QSAR models-strategies and importance. International Journal of Drug Design & Discovery, 3, 511-519.

Wang, G., Peng, Z., Wang, J., Li, J., and Li, X. (2016). Synthesis and biological evaluation of novel 2, 4, 5-triarylimidazole–1, 2, 3-triazole derivatives via click chemistry as α-glucosidase inhibitors. Bioorganic & medicinal chemistry letters, 26(23), 5719-5723.

Yap, C. W. (2011). PaDEL‐descriptor: An open source software to calculate molecular descriptors and fingerprints. Journal of computational chemistry, 32(7), 1466-1474.