CP-MLR derived QSAR rationales for the PPARy agonistic activity of the pyridyloxybenzene-acylsulfonamide derivatives
DOI:
https://doi.org/10.30574/gscbps.2020.12.1.0231Keywords:
QSAR, PPARg transactivation, combinatorial protocol in multiple linear regression (CP-MLR) analysis, Dragon descriptors, Pyridyloxybenzene-acylsulfonamides.Abstract
QSAR rationales have been obtained for the PPARg transactivation activity of pyridyloxybenzene-acylsulfonamides in terms of 0D- to 2D-Dragon descriptors. The descriptors identified in CP-MLR analysis have highlighted the role of atomic mass, van der Waals volumes and polarizability through weighted 2D autocorrelations (GATS1v and GATS1p), modified Burden eigenvalue (BEHm4) and molecular weight (MW). Sum of topological distances between O and S atoms (descriptor T(O..S)), and N and Cl atoms (descriptor T(N..Cl)), average connectivity index chi-1(X1A) and Quadratic index (Qindex) have also shown dominance to optimize the PPARγ transactivation. Descriptors RBN and RBF suggested presence of rotatable bonds in a molecular structure for better PPARg activity. Applicability domain analysis revealed that the suggested model matches the high quality parameters with good fitting power and the capability of assessing external data and all of the compounds was within the applicability domain of the proposed model and were evaluated correctly.
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References
American Diabetes Association. (2004). Diagnosis and classification of diabetes mellitus. Diabetes Care, 27 (Suppl.1), S5–S10.
Wild S, Roglic G, Green A, Sicree R and King H. (2004). Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care, 27, 1047-1053.
Lehmann JM, Moore LB, S-Oliver TA, Wilkison WO, Willson TM and Kliewer SA. (1995). An antidiabetic thiazolidinedione is a high affinity ligand for peroxisome proliferator-activated receptor gamma (PPAR gamma). The Journal of Biological Chemistry, 270, 12953-12956.
Evans RM, Barish GD and Wang Y-X. (2004). PPARs and the complex journey to obesity. Nature Medicine, 10, 355-361.
Willson TM, Brown PJ, Sternbach DD and Henke BR. (2000). The PPARs: from orphan receptors to drug discovery. Journal of Medicinal Chemistry, 43, 527-550.
Berger J and Moller DE. (2002). The mechanisms of action of PPARs. Annual Review of Medicine, 53, 409-435.
Henke BR. (2004). Peroxisome proliferator-activated receptor gamma (PPARgamma) ligands and their therapeutic utility. Progress in Medicinal Chemistry, 42, 1-53.
Cho N and Momose Y. (2008). Peroxisome proliferator-activated receptor gamma agonists as insulin sensitizers: from the discovery to recent progress. Current Topics in Medicinal Chemistry, 8, 1483-1507.
Berger JP, Akiyama TE and Meinke PT. (2005). PPARs: therapeutic targets for metabolic disease. Trends in Pharmacological Sciences, 26, 244-251.
Loviscach M, Rehman N, Carter L, Mudaliar S, Mohadeen P, Ciaraldi TP, Veerkamp JH and Henry RR. (2000). Distribution of peroxisome proliferator-activated receptors (PPARs) in human skeletal muscle and adipose tissue: relation to insulin action. Diabetlogia, 43, 304-311.
Minoura H, Takeshita S, Ita M, Hirosumi J, Mabuchi M, Kawamura I, Nakajima S, Nakayama O, Kayakiri H, Oku T, Okubo-Suzuki A, Fukagawa M, Kojo H, Hanioka K, Yamasaki N, Imoto T, Kobayashi Y and Mutoh S. (2004). Pharmacological characteristics of a novel non-thiazolidinedione insulin sensitizer, FK614. European Journal of Pharmacology, 494, 273-281.
Minoura H, Takeshita S, Yamamoto T, Mabuchi M, Hirosumi J, Takakura S, Kawamura I, Seki J, Manda T, Ita, M and Mutoh S. (2005). Ameliorating effect of FK614, a novel non-thiazolidinedione peroxisome proliferator-activated receptor gamma agonist, on insulin resistance in Zucker fatty rat. European Journal of Pharmacology, 519, 182-190.
Kyowa Hakko Kirin Company Limited. Yanagisawa A, Otsubo W, Ueno K, Suzuki M, Matsubara M, Saeki S, Yao K, Hamaguchi A and Aratake S. (2008). Biphenyl derivative.
Kowa Company Limited. Miura T, Onogi K, Gomi N, Araki T, Tagashira J, SekimotoR, Ishida R, Aoki H and Ohgiya T. (2011). Novel sulfonamide derivative and pharmaceutical product containing same. PCT Int. Appl. WO2011/024468.
Hopkins CR, O’Neil SV, Laufersweiler MC, Wang Y, Pokross M, Mekel M, Evdokimov A, Walter R, Kontoyianni M, Petrey ME, Sabatakos G, Roesgen JT, Richardson E and Demuth TP. (2006). Design and synthesis of novel N-sulfonyl-2-indole carboxamides as potent PPAR-gamma binding agents with potential application to the treatment of osteoporosis. Bioorganic and Medicinal Chemistry Letters, 16, 5659-5663.
Etgen GJ and Mantlo N. (2003). PPAR ligands for metabolic disorders. Current Topics in Medicinal Chemistry, 3, 1649.
Rikimaru K, Wakabayashi T, Abe H, Imoto H, Maekawa T, Ujikawa O, MuraseK, Matsuo T, Matsumoto M, Nomura C, Tsuge H, Arimura N; Kawakami K, Sakamoto J, Funami M, Mol CD, Snell GP, Bragstad KA, Sang B-C,Dougan DR, Tanaka T, Katayama N, Horiguchi Y and Momose Y. (2012). A new class of non-thiazolidinedione, non-carboxylic-acid-based highly selective peroxisome proliferator-activated receptor (PPAR) agonists: Design and synthesis of benzylpyrazole-acylsulfonamides. Bioorganic and Medicinal Chemistry, 20, 714-733.
Rikimaru K, Wakabayashi T, Abe H, Tawaraishi T, Imoto H, Yonemori J, Hirose H, Murase K, Matsuo T, Matsumoto M, Nomura C, Tsuge H, Arimura N, Kawakami K, Sakamoto J, Funami M, Mol CD, Snell GP, Bragstad KA, Sang B-C, Dougan DR, Tanaka T, Katayama N, Horiguchi Y and Momose Y. (2012). Structure–activity relationships and key structural feature of pyridyloxybenzene-acylsulfonamides as new, potent, and selective peroxisome proliferator-activated receptor (PPAR) agonists. Bioorganic and Medicinal Chemistry, 20, 3332–3358.
Momose Y, Maekawa T, Yamano T, Kawada M, Odaka H, Ikeda H and Sohda T. (2002). Novel 5-substituted 2,4-thiazolidinedione and 2,4-oxazolidinedione derivatives as insulin sensitizers with antidiabetic activities. Journal of Medicinal Chemistry, 45, 1518-1534.
Chemdraw ultra 6.0 and Chem3D ultra, Cambridge Soft Corporation, Cambridge, USA. http://www.cambridgesoft.com
Dragon software (version 1.11-2001) by Todeschini R.; Consonni V. Milano, Italy. http://www.talete.mi.it/dragon.htm
Prabhakar YS. (2003). A combinatorial approach to the variable selection in multiple linear regression: analysis of Selwood et al. Data Set-a case study. QSAR and Combinatorial Science, 22, 583-595.
Sharma S, Prabhakar YS, Singh P and Sharma BK. (2008). QSAR study about ATP-sensitive potassium channel activation of cromakalim analogues using CP-MLR approach. European Journal of Medicinal Chemistry, 43, 2354-2360.
Sharma S, Sharma BK, Sharma SK, Singh P and Prabhakar YS. (2009). Topological descriptors in modeling the agonistic activity of human A3 adenosine receptor ligands: The derivatives of 2-Chloro-N6-substituted-4'-thioadenosine-5'-uronamide. European Journal of Medicinal Chemistry, 44, 1377-1382.
Sharma BK, Pilania P, Singh P and Prabhakar YS. (2010). Combinatorial protocol in multiple linear regression/partial least-squares directed rationale for the caspase-3 inhibition activity of isoquinoline-1,3,4-trione derivatives. SAR and QSAR in Environmental Research, 21, 169-185.
Sharma BK, Singh P, Sarbhai K and Prabhakar YS. (2010). A quantitative structure-activity relationship study on serotonin 5-HT6 receptor ligands: Indolyl and piperidinyl sulphonamides. SAR and QSAR in Environmental Research, 21, 369-388.
Topliss JG and Edwards RP. (1979). Chance factors in studies of quantitative structure–activity relationships. Journal of Medicinal Chemistry, 22, 1238–1244.
Katritzky AR, Dobchev DA, Slavov S and Karelson M. (2008). Legitimate utilization of large descriptor pools for QSAR/QSPR models. Journal of Chemical Information and Modeling, 48, 2207–2213.
So S-S and Karplus M. (1997). Three-dimensional quantitative structure–activity relationship from molecular similarity matrices and genetic neural networks. 1. Method and validation. Journal of Medicinal Chemistry, 40, 4347–4359.
Prabhakar YS, Solomon VR, Rawal RK, Gupta MK and Katti SB. (2004). CP-MLR/PLSdirected structure–activity modeling of the HIV-1 RT inhibitory activity of 2,3-diaryl-1,3-thiazolidin-4-ones. QSAR and Combinatorial Science. 23, 234-244.
Akaike H. (1973). Information theory and an extension of the minimum likelihood principle. In: Petrov BN and Csaki F. (Eds.). Second international symposium on information theory. Budapest: Akademiai Kiado, 267–281.
Akaike H. (1974). A new look at the statistical identification model. IEEE Transactions on Automatic Control, AC-19, 716–723.
Kubinyi H. (1994). Variable selection in QSAR studies. I. An evolutionary algorithm. Quantitative Structure-Activity Relationship, 13, 285–294.
Kubinyi H. (1994). Variable selection in QSAR studies. II. A highly efficient combination of systematic search and evolution. Quantitative Structure-Activity Relationship, 13, 393–401.
Friedman J. (1990). In Technical Report No. 102. Laboratory for Computational Statistics, Stanford University: Stanford.
Gramatica P. (2007). Principles of QSAR models validation: internal and external. QSAR and Combinatorial Science, 26, 694-701.
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