MOLECULAR DOCKING AND QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP (QSAR) STUDIES OF SOME SELECTED ANTI-ULCER INHIBITORS
DOI:
https://doi.org/10.18540/jcecvl5iss1pp0100-0110Keywords:
K /H AT-pase, QSAR, GFA, DFT, PUD (B3LYP/6-31G*)Abstract
Proton pump inhibitors portray the first choice for treating various ulcer diseases, because they inhibits H+/K+-ATpase enzyme by covalently binding to cysteine residue of either potassium or proton pump. therefore, this enzyme is a validated target for anti-ulcer drugs. A quantitative structure-activity relationship and molecular docking studies have been made on 30 benzo[d]thiazole series as H+/K+-ATPase inhibitors. Density Functional Theory was used to optimised the geometry of the anti-ulcer compounds. Four types of molecular descriptors were generated in other to know the relationship that exit between anti-ulcer activity and structural properties of these compounds. The QSAR result revealed a high statistically significant correlation coefficients R2 = 0.9401, R2adj = 0.9250, Q2LOO = 0.8842 and R2 pred= 0.7975, our QSAR model showed an excellent predictive activity with chemical property of the compounds, the results of the docking analysis revealed that most of the compounds show very good relation with the active receptor, with a better docking score of -9.1kcal/mol. The physicochemical parameters are to be considered when improving the inhibitory activities of benzo[d]thiazole against the enzyme that cause ulcer (H+/K+-ATPase).
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Abdulfatai, U.; Uzairu, A.; & Uba, S. Molecular docking and quantitative structure-activity relationship study of anticonvulsant activity of aminobenzothiazole derivatives. Beni-Suef University Journal of Basic and Applied Sciences (2017).
Arthur, D. E.; Uzairu, A.; Mamza, P.; Abechi, S. E.; & Shallangwa, G. Insilico Modelling of Quantitative Structure-Activity Relationship of Pgi50 Anticancer Compounds on k-562 Cell Line. Cogent Chemistry, 1432520 (2018).
Anand, K.; & Wakode, S.; Development of drugs based on Benzimidazole Heterocycle: Recent advancement and insights. IJCS, 5(2), 350-362 (2017).
Anonymous. Wave function. Inc. Spartan’14 (Version 1.1.2). Irvine, CA. 2013.
Chaudary, S.; Kaila A.; Sharma R. B.; Vashist H.; (2015). A review on peptic ulcer, International journal of recent advances in Sciences and technology, 2 6-10 (2015).
DRINI, M.; 2017. Peptic ulcer disease and non-steroidal anti-inflammatory drugs. Australian prescriber, 40, 91. (2017).
Fashner, J.; & Gitu, A. C.; (2015). Diagnosis and Treatment of Peptic Ulcer Disease and H. pylori Infection. American family physician, 91(4) 2015.
Jalali-Heravi, M.; & Kyani, A.; (2004). Use of computer-assisted methods for the modeling of the retention time of a variety of volatile organic compounds: a PCA-MLR-ANN approach. Journal of chemical information and computer sciences, 44(4), 1328-1335 (2004).
Kaur, D.; Rana, A.; Sharma, N.; & Kumar, S.; (2012). Herbal drugs with anti ulcer activity.
Kennard, R. W., & Stone, L. A. (1969). Computer aided design of experiments. Technometrics, 11(1), 137-148 (2012).
KOUITCHEU MABEKU, L. B.; NANFACK NANA, B.; EYOUM BILLE, B.; TCHUENTEU TCHUENGUEM, R.; & NGUEPI, E. 2017. Anti-Helicobacter pylori and antiulcerogenic activity of Aframomum pruinosum seeds on indomethacin-induced gastric ulcer in rats. Pharmaceutical biology, 55, 929-936 (2017).
Lanas, A., & Chan, F. K. (2017). Peptic ulcer disease. The Lancet, 390(10094), 613-624.
Li, Y.-R., Li, C., Liu, J.-C., Guo, M., Zhang, T.-Y., Sun, L.-P., . . . Piao, H.-R. (2015). Synthesis and biological evaluation of 1, 3-diaryl pyrazole derivatives as potential antibacterial and anti-inflammatory agents. Bioorganic & medicinal chemistry letters, 25(22), 5052-
Noor, A.; Qazi, N. G.; Nadeem, H.; Khan, A.-u.; Paracha, R. Z.; Ali, F.; & Saeed, A. (2017). Synthesis, characterization, anti-ulcer action and molecular docking evaluation of novel benzimidazole-pyrazole hybrids. Chemistry Central Journal, 11(1), 85 (2017).
Rajesh, R.; Manikandan, A.; Sivakumar, A.; Ramasubbu, C.; & Nagaraju, N.; (2017). Substituted methoxybenzyl-sulfonyl-1H-benzo [d] imidazoles evaluated as effective H+/K+-ATPase inhibitors and anti-ulcer therapeutics. European journal of medicinal chemistry, 139, 454-460 (2017).
Rakesh, K. P.; Darshini, N.; Vidhya, S. L.; & Mallesha, N.; (2017). Synthesis and SAR studies of potent H+/K+-ATPase and anti-inflammatory activities of symmetrical and unsymmetrical urea analogues. Medicinal Chemistry Research, 26(8), 1675-1681 (2017).
Shi, W.-K.; Deng, R.-C.; Wang, P.-F.; Yue, Q.-Q.; Liu, Q.; Ding, K.-L.; . . . Deng, M. (2016). 3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation. Bioorganic & medicinal chemistry, 24(19), 4519-4527 (2016)
Skoglund, A.; (2008). Mechanisms of genetic adaptation in Helicobacter pylori: Institutionen för mikrobiologi, tumör-och cellbiologi/Department of Microbiology, Tumor and Cell Biology (2008).
Shamsuddeen, U.; Yusha’u, M.; & Adamu, I.; (2009). Helicobacter pylori: the causative agent of peptic ulcer. Bayero Journal of Pure and Applied Sciences, 2(2), 79-83 (2009).
Tropsha, A.; Gramatica, P.; & 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 (2003).
TROTT, O.; & 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, 455-461 (2011)
UTZERI, E.; & USAI, P.; 2017. Role of non-steroidal anti-inflammatory drugs on intestinal permeability and nonalcoholic fatty liver disease. World journal of gastroenterology, 23, 3954 (2011).
Veerasamy, R.; Rajak, H.; Jain, A.; Sivadasan, S.; Varghese, C. P.; & Agrawal, R. K.; (2011). Validation of QSAR models-strategies and importance. International Journal of Drug Design & Discovery, 3, 511-519 (2011).
Wang, S.-M.; Zha, G.-F.; Rakesh, K.; Darshini, N., Shubhavathi, T.; Vivek, H.; Qin, H.-L. (2017). Synthesis of benzo [d] thiazole-hydrazone analogues: molecular docking and SAR studies of potential H+/K+ ATPase inhibitors and anti-inflammatory agents. MedChemComm, 8(6), 1173-1189 (2017).
YAP, C. W.; 2011. PaDEL‐descriptor: An open source software to calculate molecular descriptors and fingerprints. Journal of computational chemistry, 32, 1466-1474 (2011).
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