Pasha, F. A. Muddassar, M. Jung, Hwanwon Yang, Beom-Seok Lee, Cheolju Oh, Jung Soo Cho, Seung Joo Cho, Hoon 2024-01-20T23:33:26Z 2024-01-20T23:33:26Z 2021-09-03 2008-03-20 0253-2964 https://pubs.kist.re.kr/handle/201004/133644 Microsomal prostaglandin E-2 synthase (mPGES-1) is a potent target for pain and inflammation. Various QSAR (quantitative structure activity relationship) analyses used to understand the factors affecting inhibitory potency for a series of MK886 analogues. We derived four QSAR models utilizing various quantum mechanical (QM) descriptors. These QM models indicate that steric, electrostatic and hydrophobic interaction can be important factors. Common pharmacophore hypotheses (CPHs) also have studied. The QSAR model derived by best-fitted CPHs considering hydrophobic, negative group and ring effect gave a reasonable result (q(2) = 0.77, r(2) = 0.97 and R-testset = 0.90). The pharmacophore-derived molecular alignment subsequently used for 3D-QSAR. The CoMFA (Comparative Molecular Field Analysis) and CoMSIA (Comparative Molecular Similarity Indices Analysis) techniques employed on same series of mPGES-1 inhibitors which gives a statistically reasonable result (CoMFA; q(2) = 0.90, r(2) = 0.99. CoMSIA; q(2) = 0.93, r(2) = 1.00). All modeling results (QM-based QSAR, pharmacophore modeling and 3D-QSAR) imply steric, electrostatic and hydrophobic contribution to the inhibitory activity. CoMFA and CoMSIA models suggest the introduction of bulky group around ring B may enhance the inhibitory activity. English KOREAN CHEMICAL SOC PROSTAGLANDIN E-2 SYNTHASE ATOMIC PHYSICOCHEMICAL PARAMETERS DIRECTED QUANTITATIVE STRUCTURE 5-LIPOXYGENASE-ACTIVATING PROTEIN LEUKOTRIENE C-4 INHIBITORS COMFA COMSIA IDENTIFICATION REACTIVITY QM and pharmacophore based 3D-QSAR of MK886 analogues against mPGES-1 Article 1 BULLETIN OF THE KOREAN CHEMICAL SOCIETY, v.29, no.3, pp.647 - 655 BULLETIN OF THE KOREAN CHEMICAL SOCIETY 29 3 647 655 scie scopus kci ART001238495 000255229900024 2-s2.0-41549154195 Chemistry, Multidisciplinary Chemistry Article PROSTAGLANDIN E-2 SYNTHASE ATOMIC PHYSICOCHEMICAL PARAMETERS DIRECTED QUANTITATIVE STRUCTURE 5-LIPOXYGENASE-ACTIVATING PROTEIN LEUKOTRIENE C-4 INHIBITORS COMFA COMSIA IDENTIFICATION REACTIVITY 3D-QSAR drug design CoMFA CoMSIA mPGES-1