QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP AND MOLECULAR DOCKING STUDIES OF HYDROXAMIC ACID DERIVATIVES AS NOVEL CLASS INHIBITORS AGAINST HELICOBACTER PYLORI UREASE
In order to develop quantitative structure-activity relationship (QSAR), for predicting antiulcer activity of hydroxamic acid analogues use as dataset and their antiulcer activity were obtained from the literature. Density Functional Theory (DFT) using B3LYP/6-31G* quantum chemical calculation method was used to find the optimized geometry of the studied compounds. Eight types of molecular descriptors were used to find out the relation between antipeptic ulcer (APU) activity and structural properties. Relevant molecular descriptors were selected by Genetic Function Algorithms (GFA). The best model obtained was given a distinct validated, good and robust statistical parameters which include; square correlation coefficient R2 value of (0.9989), adjusted determination coefficient, R2adj value of (0.9984), Leave one out cross validation determination coefficient Q2 value of (0.9948) and external validation as predicted determination coefficient R2 value of(0.8409). Molecular docking analysis find out that, the best lead-compound with the higher negative value score of (-8.5 kcal/mol) were formed hydrophobic interaction and H-bonding with amino acid residue between the inhibitors compounds with their respective receptor.
Ezealisiji KM, Ijeomah SC, Agbo MO, Anti-ulcer activity of African walnut Tetracarpidium conophorum nuts against gastric ulcers in rats. Asian Pac J Trop Dis 2014 4:998–1001
Sharma D, Bhatt SA, Comprehensive review on ulcer healing potential of medicinal plants. Int J Pharm Pharm Sci 2014 6:10
Amtul Z, Siddiqui RA, Choudhary MI, Chemistry and mechanism of urease in- hibition. Curr Med Chem 2002 9:1323–48
Yamasaki E, Wada A, Kumatori A, et al. Helicobacter pylori vacuolating cytotoxin induces activation of the proapoptotic proteins Bax and Bak, leading to cytochrome c release and cell death, independent of vacuolation. J Biol Chem 2006 281: 11250-11259
Radin JN, González-Rivera C, Frick-Cheng AE, Sheng J, Gaddy JA, Rubin DH, Scott Algood HM, McClain MS, Cover TL. Role of connexin 43 in Helicobacter pylori VacA-induced cell death. J. Infect. Immun. 2013; 82: 423-32.
Chey, W.; Chathadi, K.; Montague, J.; Ahmed, F.; Murthy, U. Intragastric acidification reduces the occurrence of false-negative urea breath test results in patients taking a proton pump inhibitor. Am. J. Gastroent. 2001; 96(4): 1028-32.; Hunter, P. Where next for antibiotics? The immune system and the nature of pathogenicity are providing vital clues in the fight against antibiotic‐resistant bacteria. EMBO Rep. 2012; 13: 680-3.
Simmons, K. J.; Chopra, I.; Fishwick, C. W. Structure-based discovery of antibacterial drugs. Nature Reviews Microbiology. 2010; 501-10.; Lodhi MA, Nawaz SA, Iqbal S, Khan KM, Rode BM, Choudhary MI. 3D-QSAR CoMFA studies on bis-coumarine analogues as urease inhibitors: A strategic design in anti-urease agents. Bioorg. Med. Chem. 2008; 16(6): 3456-61.
Sachs G, Weeks DL, Wen Y, Marcus EA, Scott DR, Melchers K. Acid acclimation by Helicobacter pylori. Physiology (Bethesda). 2005; 20: 429-38.
Stingl K, Altendorf K, Bakker EP. Acid survival of Helicobacter pylori: how does urease activity trigger cytoplasmic pH homeostasis? Trends in microbiol. 2002; 10(2): 70-4; Maroney MJ, Ciurli S. Nonredox Nickel Enzymes. Chem. Rev. 2013; 114(8): 4206-28.
Saeed A, Tehseen Y, Rafique H, Furtmann N, Bajorath J. Benzothiazolyl substituted iminothiazolidinones and benzamido-oxothiazolidines as potent and partly selective aldose reductase inhibitors. Med. Chem. Commun. 2014; 5: 1371-80; Azizian H, Nabati F, Sharifi A, Siavoshi F, Mahdavi M, Amanlou M. Large-scale virtual screening for the identification of new Helicobacter pylori urease inhibitor scaffolds. J. Mol. Model. 2012; 18: 2917-27.
Kosikowska, P.; Berlicki, Ł. Expert opinion on therapeutic patents, 2011 Augt 6, 21: 945
Zhang, Y.; Feng, J.; Jia, Y.; Wang, X.; Zhang, L.; Liu, C.; Fang, H.; Xu, W. Development of Tetrahydroisoquinoline-Based Hydroxamic Acid Derivatives: Potent Histone Deacetylase Inhibitors with Marked in Vitro and in Vivo Antitumor Activities Journal of medicinal chemistry, 2011 Apr 5, 54: 2823.
Neelarapu, R.; Holzle, DL.; Velaparthi, S.; Bai, H.; Brunsteiner, M.; Blond, S. Y.; Petukhov, P. J. Synthesis, molecular docking and kinetic properties of β-hydroxy-β-phenylpropionyl-hydroxamic acids as Helicobacter pylori urease inhibitors, European journal of medicinal chemistry 2013 Aug 9, 68: 212.
Xiao, Z. P.; Shi, D. H.; Li, H. Q.; Zhang, L. N.; Xu, C.; Zhu, H. L. Polyphenols based on isoflavones as inhibitors of Helicobacter pylori urease. Bioorganic & medicinal chemistry. 2007 Jun 1; 15(11): 3703-10.
Wang, X. D.; Wei, W.; Wang, P. F.; Yi, L. C.; Shi, W. K.; Xie, Y. X.; Synthesis, and evaluation of novel fluoroquinoloneeflavonoid hybrids as potent antibiotics against drug-resistant microorganisms, J. Bioorganic & medicinal chemistry 2015, Oct 20, 23: 4860
Xiao, Z. P.; Peng, Z. Y.; Dong, J. J.; He, J.; Ouyang, H.; Feng, Y. T.; Lu, C. L.; Lin, W. Q.; Wang, J.X.; Xiang, Y. P.; Structure-activity relationship analysis and kinetics study of reductive derivatives of flavonoids as Helicobacter pylori urease inhibitors. European journal of medicinal chemistry 2013 May; 63:685-95. Peng, Z. Y.; Wang, X. D.; Feng, Y. T.; He, J.; Xiao, Z. P.; Biological evaluation and molecular modeling of 1,3,4-thiadiazol-2-amide derivatives as novel antitubulin agents. Journal of Jishou University (Natural Sciences Edition) 2012, Jun 6, 021
Kubo, J.; Lee, J. R.; Kubo, I. Anti-Helicobacter pylori Agents from the Cashew Apple, Journal of Agricultural and Food Chemistry 1999, Jun 6, 47, 533
Xiao, Z. P.; Wang, X. D.; Peng, Z. Y.; Huang, S.; Yang, P.; Li, Q. S.; Zhou, L. H.; Hu, X. J.; Wu, L. J.; Zhou, Y. Dilatational Rheology of Heat-Treated Soy Protein at the Oil–Water Interface: Relationship to Structural Properties, Journal of agricultural and food chemistry 2012, Nov 1 60: 10572.
Kubinyi, H. (1993). QSAR Hanch Analysis & Related ApproachES. In H. Kubinyi. Tokyo, Japan: VCH, New York, USA.
Hugo Kubinyi. Applications of Hansch Analysis.; QSAR, Hanch Analysis and Related Approaches VCH 1993, 5-(6), 567
Puzyn, J. L. challenges and advances in computational chemistry and physics tomasz. in recent advances in qsar studies london, new york: springer dordrecht heidelberg. 2010. feb 3 (vol. 8, pp. 5-7).
Jitender K. Malik, Himesh S.; Singhai AK,; Harish P.; hydroxamic acids as Helicobacter pylori urease inhibitors, International Journal of Phermaceutical Research & Allies Science 2013, Feb 2; 2, 1
Yap CW. PaDEL-descriptor: open source software to calculate molecular descriptors and ingerprints. J Comput Chem 2011 Jul 9; 32 (7):1466–74.
Kennard RW, Stone LA. Computer aided design of experiments, Journal of Technometrics 1969, Sep 7; 11(1):137–48.
Khaled KF. Modeling corrosion inhibition of iron in acid medium by genetic function approximation method: a QSAR model. Journal of Corro Sci 2011; 53(11):3457–65
Wang, X. D.; Wei, W.; Wang, P. F.; Yi, L. C.; Shi, W. K.; Xie, Y. X.; Wu, L. Z.; Tang, N.; Zhu, L. S.; Peng, J. Synthesis, molecular docking and biological evaluation of 3-arylfuran-2(5H)-ones as anti-gastric ulcer agent. Bioorganic & medicinal chemistry 2015, Aug 1. 23, 4860
Ravinchandran R.; V., Jain., H.; Sivansan.; A.; VargheseS.; Kishore, Agrawal.; R.; Characterization of pioglitazone cyclodextrin complexes Int. J. of Drug Design and Discov, 2011, Nov. 7.; 2:511-519
Monika JK, Singh K. Virtual screening using the ligand ZINC database for novel lipoxygenase-3 inhibitors. Bioinformation. 2013; 9(11):583.
Trott O, Olson AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 2010 Jun 5; 31:455–61.
Kumar DB, Kumar PV, Bhubaneswaran SP, Mitra A. Advanced drug designing softwares and their application in medical research. Int J Pharm Sci 2010 Apr 23; 2:16–8.
Mallesha*b and Hua-Li Qin*a et al, Synthesis and molecular docking studies of xanthone attached amino acids as potential antimicrobial and anti-inflammatory agents, J. MedChemComm, 2017 Aug 1; 8(8): 1706–1719.
Anonymous. Wavefunction. Inc., Spartan’14, version 1.1.2. Irvine, California, USA; 2013.
Ravinchandran Rajak V, Jain H, Sivadasan A, Varghese S, Kishore-Agrawal CP. Quantitative structure–activity relationship (QSAR) for predicting the anticonvulsant activity of α_substituted acetamido-N-benzylacetamide derivatives R Int J Drug Des Discov 2011 Apr 16;2:511–9.
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