QSAR STUDY ON p38 MITOGEN ACTIVATED PROTEIN KINASE - INHIBITION FOR BRONCHIAL ASTHMA

  Rayan Ahmed

Asthma is a disease of the airways caused by chronic inflammation, elevated serum IgE levels, airway hyperresponsiveness and, frequently, airway remodelling. T-helper type 2 cells together with mast cells, B cells, and eosinophils as well as inflammatory cytokines and chemokines are proposed to play a critical role in the initiation and perpetuation of allergic asthma. therefore, the inhibition of p38 MAPK is a lucrative therapeutic strategy for the treatment of asthma. The p38 MAPK are activated using variety of stimuli. A large dataset of 2,186 compounds with reported IC50 values against MAPK p38α was obtained from ChEMBL database and induced in quantitative structure-activity relationship study so as to gain insights on their origin of bioactivity. MAPK p38 α were described by a set of 12 fingerprint descriptors and predictive models were constructed from regressor comparison best model where selected and further tuned to give better performance. It was observed that several 12 fingerprint descriptors afforded good performance were in R2 0.32 – 0.63, Q2CV 0.24 – 0.53 and Q2Ext 0.26 – 0.55 for the training set. It is anticipated that our proposed QSAR model may become a useful high-throughput tool for identifying novel inhibitors against p38 MAPKs. Conclusion: Twelve sets of fingerprint descriptors were used for constructing QSAR models and their performances were comparatively evaluated. It was observed that several fingerprint descriptors afforded good performance for the constructed models indicating that they could capture the feature space of p38 MAPKs inhibitors. By taking advantage of the built-in feature importance estimator and SHAP Library plots, the following important features that are for MAPKs inhibition were identified: SubFPC301(1,5-Tautomerizable), SubFPC295(C ONSbond), SubFPC274(Aromatic ring) and SubFPC181(HeteroNnonbasic). Results from molecular docking also support the aforementioned findings from the QSAR models in which the aromatic, and heteroaromatic rings were preferable moieties for interacting with the hydrophobic pocket of p38 MAPKα. It is anticipated that the knowledge gained from this study could be used as general guidelines for the design of novel p38 MAPKα inhibitors.

Keywords- QSAR study, Docking study, p38 MAPK, Inhibitor, Asthma, Data Science

Unique Identification Number - IJEDR2301007
Page Number(s) - 40-60
Pubished in - Volume 11 | Issue 1 | January 2023
DOI (Digital Object Identifier) -    http://doi.one/10.1729/Journal.33562
Publisher - IJEDR (ISSN - 2321-9939)

  Rayan Ahmed,   "QSAR STUDY ON p38 MITOGEN ACTIVATED PROTEIN KINASE - INHIBITION FOR BRONCHIAL ASTHMA", International Journal of Engineering Development and Research (IJEDR), ISSN:2321-9939, Volume.11, Issue 1, pp.40-60, January 2023, Available at :http://www.ijedr.org/papers/IJEDR2301007.pdf