Molecular Docking and Dynamics Simulation Analysis of Thymoquinone and Thymol Compounds from Nigella sativa L. that Inhibit Cag A and Vac A Oncoprotein of Helicobacter pylori: Probable Treatment of H. pylori Infections

Author(s): Heena Tabassum, Iffat Zareen Ahmad*

Journal Name: Medicinal Chemistry

Volume 17 , Issue 2 , 2021


Become EABM
Become Reviewer
Call for Editor

Graphical Abstract:


Abstract:

Background: Helicobacter pylori infection is accountable for most of the peptic ulcer and intestinal cancers. Due to the uprising resistance towards H. pylori infection through the present and common proton pump inhibitors regimens, the investigation of novel candidates is the inevitable issue. Medicinal plants have always been a source of lead compounds for drug discovery. The research of the related effective enzymes linked with this gram-negative bacterium is critical for the discovery of novel drug targets.

Objective: The aim of the study is to identify the best candidate to evaluate the inhibitory effect of thymoquinone and thymol against H. pylori oncoproteins, Cag A and Vac A in comparison to the standard drug, metronidazole by using a computational approach.

Materials and Methods: The targeted oncoproteins, Cag A and Vac A were retrieved from RCSB PDB. Lipinski’s rule and ADMET toxicity profiling were carried out on the phytoconstituents of the N. sativa. The two compounds of N. sativa were further analyzed by molecular docking and MD simulation studies. The reported phytoconstituents, thymoquinone and thymol present in N. sativa were docked with H. pylori Cag A and Vac A oncoproteins. Structures of ligands were prepared using ChemDraw Ultra 10 software and then changed into their 3D PDB structures using Molinspiration followed by energy minimization by using software Discovery Studio client 2.5.

Results: The docking results revealed the promising inhibitory potential of thymoquinone against Cag A and Vac A with docking energy of -5.81 kcal/mole and -3.61kcal/mole, respectively. On the contrary, the inhibitory potential of thymol against Cag A and Vac A in terms of docking energy was -5.37 kcal/mole and -3.94kcal/mole as compared to the standard drug, metronidazole having docking energy of -4.87 kcal/mole and -3.20 kcal/mole, respectively. Further, molecular dynamic simulations were conducted for 5ns for optimization, flexibility prediction, and determination of folded Cag A and Vac A oncoproteins stability. The Cag A and Vac A oncoproteins-TQ complexes were found to be quite stable with the root mean square deviation value of 0.2nm.

Conclusion: The computational approaches suggested that thymoquinone and thymol may play an effective pharmacological role to treat H. pylori infection. Hence, it could be summarized that the ligands thymoquinone and thymol bound and interacted well with the proteins Cag A and Vac A as compared to the ligand MTZ. Our study showed that all lead compounds had good interaction with Cag A and Vac A proteins and suggested them to be a useful target to inhibit H. pylori infection.

Keywords: N. sativa, phytoconstituents, hepatocellular carcinoma, molecular docking, simulation, H. pylori.

[1]
Sayehmiri, F.; Darvishi, Z.; Sayehmiri, K.; Soroush, S.; Emaneini, M.; Zarrilli, R.; Taherikalani, M. A systematic review and meta-analysis study to investigate the prevalence of Helicobacter pylori and the sensitivity of its diagnostic methods in Iran. Iran. Red Crescent Med. J., 2014, 16(6)e12581
[http://dx.doi.org/10.5812/ircmj.12581 ] [PMID: 25068041]
[2]
Longo, D.; Fauc, A.; Kasper, D.; Hauser, S.; Jameson, J.; Loscalzo, J. Harrison’s Principles of Internal Medicine; 18th ed.; USA, Mc Graw Hill, 2012, 18, p. e23771..
[3]
Chey, W.D.; Wong, B.C. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am. J. Gastroenterol., 2007, 102(8), 1808-1825.
[http://dx.doi.org/10.1111/j.1572-0241.2007.01393.x ] [PMID: 17608775]
[4]
Khan, M.K.A.; Siddiqui, M.H.; Akhtar, S.; Ahmad, K.; Baig, M.H.; Osama, K. Screening of plant-derived natural compounds as potent chemotherapeutic agents against breast cancer: An in silico approach. J. Chem. Pharm. Res., 2015, 7, 519-526.
[5]
Tepes, B.; O’Connor, A. Gisbert, J.P.; O’Morain, C. Treatment of Helicobacter pylori infection. Helicobacter, 2012, 17, 36-42.
[http://dx.doi.org/10.1111/j.1523-5378.2012.00981.x ] [PMID: 22958154]
[6]
Khaleghi, S.; Taher, M.T.; Naghibi, S.S.; Naghibi, S.M. Comparison ofsequential and routine four drugs therapeutic regiments in Helicobacter pylori eradication. J. Gorgan. Uni. Med. Sci., 2013, 15, 1-6.
[7]
Duck, W.M.; Sobel, J.; Pruckler, J.M.; Song, Q.; Swerdlow, D.; Friedman, C.; Sulka, A.; Swaminathan, B.; Taylor, T.; Hoekstra, M.; Griffin, P.; Smoot, D.; Peek, R.; Metz, D.C.; Bloom, P.B.; Goldschmidt, S.; Parsonnet, J.; Triadafilopoulos, G.; Perez-Perez, G.I.; Vakil, N.; Ernst, P.; Czinn, S.; Dunne, D.; Gold, B.D. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg. Infect. Dis., 2004, 10(6), 1088-1094.
[http://dx.doi.org/10.3201/eid1006.030744 ] [PMID: 15207062]
[8]
Shakeri, F.; Gholamnezhad, Z.; Mégarbane, B.; Rezaee, R.; Boskabady, M.H. Gastrointestinal effects of Nigella sativa and its main constituent, thymoquinone: a review. Avicenna J. Phytomed., 2016, 6(1), 9-20.
[PMID: 27247918]
[9]
Ahmad, A.; Husain, A.; Mujeeb, M.; Khan, S.A.; Najmi, A.K.; Siddique, N.A.; Damanhouri, Z.A.; Anwar, F. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3(5), 337-352.
[http://dx.doi.org/10.1016/S2221-1691(13)60075-1 ] [PMID: 23646296]
[10]
Venkatachallam, S.K.T.; Pattekhan, H. Divakar; Kadimi U.S. Chemical composition of Nigella sativa L. seed extracts obtained by supercritical carbon dioxide. J. Food Sci. Technol., 2010, 2010(47), 598-605.
[http://dx.doi.org/10.1007/s13197-010-0109-y]
[11]
Topcagic, A.; Cavar Zeljkovic, S.; Karalija, E.; Galijasevic, S.; Sofic, E. Evaluation of phenolic profile, enzyme inhibitory and antimicrobial activities of Nigella sativa L. seed extracts. Bosn. J. Basic Med. Sci., 2017, 17(4), 286-294.
[PMID: 28590231]
[12]
Hashem-Dabaghian, F.; Agah, S.; Taghavi-Shirazi, M.; Ghobadi, A. Combination of Nigella sativa and honey in eradication of gastric Helicobacter pylori infection. Iran. Red Crescent Med. J., 2016, 18(11)e23771
[http://dx.doi.org/10.5812/ircmj.23771 ] [PMID: 28191328]
[13]
Nzeako, B.C.; Al-Kharousi, Z.S.N.; Al-Mahrooqui, Z. Antimicrobial activities of clove and thyme extracts. Sultan Qaboos Univ. Med. J., 2006, 6(1), 33-39.
[PMID: 21748125]
[14]
Fock, K.M.; Talley, N.; Moayyedi, P.; Hunt, R.; Azuma, T.; Sugano, K.; Xiao, S.D.; Lam, S.K.; Goh, K.L.; Chiba, T.; Uemura, N.; Kim, J.G.; Kim, N.; Ang, T.L.; Mahachai, V.; Mitchell, H.; Rani, A.A.; Liou, J.M.; Vilaichone, R.K.; Sollano, J. Asia-Pacific consensus guidelines on gastric cancer prevention. J. Gastroenterol. Hepatol., 2008, 23(3), 351-365.
[http://dx.doi.org/10.1111/j.1440-1746.2008.05314.x ] [PMID: 18318820]
[15]
Cellini, L.; Grande, R.; Di Campli, E.; Di Bartolomeo, S.; Capodicasa, S.; Marzio, L. Analysis of genetic variability, antimicrobial susceptibility and virulence markers in Helicobacter pylori identified in Central Italy. Scand. J. Gastroenterol., 2006, 41(3), 280-287.
[http://dx.doi.org/10.1080/00365520510024223 ] [PMID: 16497614]
[16]
Wei, J.; Nagy, T.A.; Vilgelm, A.; Zaika, E.; Ogden, S.R.; Romero-Gallo, J.; Piazuelo, M.B.; Correa, P.; Washington, M.K.; El-Rifai, W.; Peek, R.M.; Zaika, A. Regulation of p53 tumor suppressor by Helicobacter pylori in gastric epithelial cells. Gastroenterology, 2010, 139(4), 1333-1343.
[http://dx.doi.org/10.1053/j.gastro.2010.06.018 ] [PMID: 20547161]
[17]
Foxall, P.A.; Hu, L.T.; Mobley, H.L.T. Use of polymerase chain reaction-amplified Helicobacter pylori urease structural genes for differentiation of isolates. J. Clin. Microbiol., 1992, 30(3), 739-741.
[http://dx.doi.org/10.1128/JCM.30.3.739-741.1992 ] [PMID: 1313051]
[18]
Turbett, G.R.; Høj, P.B.; Horne, R.; Mee, B.J. Purification and characterization of the urease enzymes of Helicobacter species from humans and animals. Infect. Immun., 1992, 60(12), 5259-5266.
[http://dx.doi.org/10.1128/IAI.60.12.5259-5266.1992 ] [PMID: 1452359]
[19]
Ma, Y.; Jin, Y.Y.; Wang, Y.L.; Wang, R.L.; Lu, X.H.; Kong, D.X.; Xu, W.R. The discovery of a novel and selective inhibitor of PTP1B over TCPTP: 3D QSAR pharmacophore modeling, virtual screening, synthesis, and biological evaluation. Chem. Biol. Drug Des., 2014, 83(6), 697-709.
[http://dx.doi.org/10.1111/cbdd.12283 ] [PMID: 24418013]
[20]
Cao, C.; Wang, S.; Cui, T.; Su, X.C.; Chou, J.J. Ion and inhibitor binding of the double-ring ion selectivity filter of the mitochondrial calcium uniporter. Proc. Natl. Acad. Sci. USA, 2017, 114(14), E2846-E2851.
[http://dx.doi.org/10.1073/pnas.1620316114 ] [PMID: 28325874]
[21]
Pan, L.; Fu, T.M.; Zhao, W.; Zhao, L.; Chen, W.; Qiu, C.; Liu, W.; Liu, Z.; Piai, A.; Fu, Q.; Chen, S.; Wu, H.; Chou, J.J. Higher-Order Clustering of the Transmembrane Anchor of DR5 Drives Signaling. Cell, 2019, 176(6), 1477-1489.e14.
[http://dx.doi.org/10.1016/j.cell.2019.02.001 ] [PMID: 30827683]
[22]
Li, X.B.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Chou, K.C. Novel inhibitor design for hemagglutinin against H1N1 influenza virus by core hopping method. PLoS One, 2011, 6(11)e28111
[http://dx.doi.org/10.1371/journal.pone.0028111 ] [PMID: 22140516]
[23]
Ma, Y.; Wang, S.Q.; Xu, W.R.; Wang, R.L.; Chou, K.C. Design novel dual agonists for treating type-2 diabetes by targeting peroxisome proliferator-activated receptors with core hopping approach. PLoS One, 2012, 7(6)e38546
[http://dx.doi.org/10.1371/journal.pone.0038546 ] [PMID: 22685582]
[24]
Chou, K.C. Impacts of bioinformatics to medicinal chemistry. Med. Chem., 2015, 11(3), 218-234.
[http://dx.doi.org/10.2174/1573406411666141229162834 ] [PMID: 25548930]
[25]
Hussain, W.; Khan, Y.D.; Rasool, N.; Khan, S.A.; Chou, K.C. SPalmitoylC-PseAAC: A sequence-based model developed via Chou’s 5-steps rule and general PseAAC for identifying S-palmitoylation sites in proteins. Anal. Biochem., 2019, 568, 14-23.
[http://dx.doi.org/10.1016/j.ab.2018.12.019 ] [PMID: 30593778]
[26]
Li, F.; Zhang, Y.; Purcell, A.W.; Webb, G.I.; Chou, K.C.; Lithgow, T.; Li, C.; Song, J. Positive-unlabelled learning of glycosylation sites in the human proteome. BMC Bioinformatics, 2019, 20(1), 112.
[http://dx.doi.org/10.1186/s12859-019-2700-1 ] [PMID: 30841845]
[27]
Chou, K.C. Progresses in predicting posttranslational modification. Int. J. Pept. Res. Ther., 2020, 26, 873-888.
[http://dx.doi.org/10.1007/s10989-019-09893-5]
[28]
Xiao, X.; Min, J.L.; Lin, W.Z.; Liu, Z.; Cheng, X.; Chou, K.C. iDrug-Target: predicting the interactions between drug compounds and target proteins in cellular networking via benchmark dataset optimization approach. J. Biomol. Struct. Dyn., 2015, 33(10), 2221-2233.
[http://dx.doi.org/10.1080/07391102.2014.998710 ] [PMID: 25513722]
[29]
Jia, J.; Liu, Z.; Xiao, X.; Liu, B.; Chou, K.C. iPPI-Esml: An ensemble classifier for identifying the interactions of proteins by incorporating their physicochemical properties and wavelet transforms into PseAAC. J. Theor. Biol., 2015, 377, 47-56.
[http://dx.doi.org/10.1016/j.jtbi.2015.04.011 ] [PMID: 25908206]
[30]
Liu, Z.; Xiao, X.; Qiu, W.R.; Chou, K.C. iDNA-Methyl: identifying DNA methylation sites via pseudo trinucleotide composition. Anal. Biochem., 2015, 474, 69-77.
[http://dx.doi.org/10.1016/j.ab.2014.12.009 ] [PMID: 25596338]
[31]
Chen, W.; Feng, P.M.; Lin, H.; Chou, K.C. iRSpot-PseDNC: identify recombination spots with pseudo dinucleotide composition. Nucleic Acids Res., 2013, 41(6)e68
[http://dx.doi.org/10.1093/nar/gks1450 ] [PMID: 23303794]
[32]
Lin, H.; Deng, E.Z.; Ding, H.; Chen, W.; Chou, K.C. iPro54-PseKNC: a sequence-based predictor for identifying sigma-54 promoters in prokaryote with pseudo k-tuple nucleotide composition. Nucleic Acids Res., 2014, 42(21), 12961-12972.
[http://dx.doi.org/10.1093/nar/gku1019 ] [PMID: 25361964]
[33]
Chou, K.C. Prediction of protein cellular attributes using pseudo amino acid composition.PROTEINS: Structure, Function, and Genetics, (Erratum: ibid., 2001, Vol.44, 60), 2001, 43, 246-255.
[34]
Chen, W.; Lei, T.Y.; Jin, D.C.; Lin, H.; Chou, K.C. PseKNC: a flexible web server for generating pseudo K-tuple nucleotide composition. Anal. Biochem., 2014, 456, 53-60.
[http://dx.doi.org/10.1016/j.ab.2014.04.001 ] [PMID: 24732113]
[35]
Chou, K.C.; Chen, N.Y. The biological functions of low-frequency phonons. Sci. Sin., 1977, 20, 447-457.
[PMID: 6487745]
[36]
Chou, K.C.; Mao, B. Collective motion in DNA and its role in drug intercalation. Biopolymers, 1988, 27(11), 1795-1815.
[http://dx.doi.org/10.1002/bip.360271109 ] [PMID: 3233332]
[37]
Chou, K.C. Low-frequency collective motion in biomacromolecules and its biological functions. Biophys. Chem., 1988, 30(1), 3-48.
[http://dx.doi.org/10.1016/0301-4622(88)85002-6 ] [PMID: 3046672]
[38]
Chou, K.C. Low-frequency resonance and cooperativity of hemoglobin. Trends Biochem. Sci., 1989, 14(6), 212-213.
[http://dx.doi.org/10.1016/0968-0004(89)90026-1 ] [PMID: 2763333]
[39]
Chou, K.C.; Chen, N.Y.; Forsen, S. The biological functions of low-frequency phonons: 2. Cooperative effects. Chem. Scr., 1981, 18, 126-132.
[40]
Chou, K.C.; Zhang, C.T.; Maggiora, G.M. Solitary wave dynamics as a mechanism for explaining the internal motion during microtubule growth. Biopolymers, 1994, 34(1), 143-153.
[http://dx.doi.org/10.1002/bip.360340114 ] [PMID: 8110966]
[41]
Madkan, A.; Blank, M.; Elson, E.; Geddis, M.S.; Goodman, R. Steps to the clinic with ELF EMF. Nat. Sci., 2009, 1, 157-165.
[http://dx.doi.org/10.4236/ns.2009.13020]
[42]
Narayanaswamy, R.; Wai, L.K.; Ismail, I.S. Molecular docking studies of quinones against human inducible nitric oxide synthase (iNOS). J. Chem. Pharm. Res., 2017, 9, 39-44.
[43]
Alam, A.; Shaikh, S.; Ahmad, S.S.; Ansari, M.A.; Shakil, S.; Rizvi, S.M.; Shakil, S.; Imran, M.; Haneef, M.; Abuzenadah, A.M.; Kamal, M.A. Molecular interaction of human brain acetylcholinesterase with a natural inhibitor huperzine-B: an enzoinformatics approach. CNS Neurol. Disord. Drug Targets, 2014, 13(3), 487-490.
[http://dx.doi.org/10.2174/18715273113126660163 ] [PMID: 24059299]
[44]
Pinto Correia, J.; Areias, M.E.; Monteiro, E.; Garnel, M.; Madeira, F. Liver cirrhosis. Clinical experience with 274 unselected cases. Digestion, 1971, 4(4), 223-233.
[http://dx.doi.org/10.1159/000197123 ] [PMID: 5317239]
[45]
Du, E.; Gan, L.; Li, Z.; Wang, W.; Liu, D.; Guo, Y. In vitro antibacterial activity of thymol and carvacrol and their effects on broiler chickens challenged with Clostridium perfringens. J. Anim. Sci. Biotechnol., 2015, 6, 58.
[http://dx.doi.org/10.1186/s40104-015-0055-7 ] [PMID: 26705471]
[46]
Duraipandiyan, V.; Ayyanar, M.; Ignacimuthu, S. Antimicrobial activity of some ethnomedicinal plants used by Paliyar tribe from Tamil Nadu, India. BMC Complement. Altern. Med., 2006, 6, 35.
[http://dx.doi.org/10.1186/1472-6882-6-35 ] [PMID: 17042964]
[47]
El-Dakhakhny, M.; Barakat, M.; El-Halim, M.A.; Aly, S.M. Effects of Nigella sativa oil on gastric secretion and ethanol induced ulcer in rats. J. Ethnopharmacol., 2000, 72(1-2), 299-304.
[http://dx.doi.org/10.1016/S0378-8741(00)00235-X ] [PMID: 10967486]
[48]
El-Dakhakhny, M.; Mady, N.; Lembert, N.; Ammon, H.P. The hypoglycemic effect of Nigella sativa oil is mediated by extrapancreatic actions. Planta Med., 2002, 68(5), 465-466.
[http://dx.doi.org/10.1055/s-2002-32084 ] [PMID: 12058330]
[49]
Ghosheh, O.A.; Houdi, A.A.; Crooks, P.A. High performance liquid chromatographic analysis of the pharmacologically active quinones and related compounds in the oil of the black seed (Nigella sativa L.). J. Pharm. Biomed. Anal., 1999, 19(5), 757-762.
[http://dx.doi.org/10.1016/S0731-7085(98)00300-8 ] [PMID: 10698539]
[50]
Obach, R.S.; Lombardo, F.; Waters, N.J. Trend analysis of a database of intravenous pharmacokinetic parameters in humans for 670 drug compounds. Drug Metab. Dispos., 2008, 36(7), 1385-1405.
[http://dx.doi.org/10.1124/dmd.108.020479 ] [PMID: 18426954]
[51]
Verma, A. Lead finding from Phyllanthus debelis with hepatoprotective potentials. Asian Pac. J. Trop. Biomed., 2012, 2, S1735-S1737.
[http://dx.doi.org/10.1016/S2221-1691(12)60486-9]
[52]
Khademi, F.; Abachi, S.; Malekzadeh, F. Microbial technologies for the Isolation and phylogenetic analysis of Marine and terrestrial bacteria with antifungal or antibacterial activities. J. Biosci. Biotechnol., 2013, 2, 25-36.
[53]
O’Gara, E.A.; Hill, D.J.; Maslin, D.J. Activities of garlic oil, garlic powder, and their diallyl constituents against Helicobacter pylori. Appl. Environ. Microbiol., 2000, 66(5), 2269-2273.
[http://dx.doi.org/10.1128/AEM.66.5.2269-2273.2000 ] [PMID: 10788416]
[54]
Sato, Y.; Oketani, H.; Singyouchi, K.; Ohtsubo, T.; Kihara, M.; Shibata, H.; Higuti, T. Extraction and purification of effective antimicrobial constituents of Terminalia chebula RETS. against methicillin-resistant Staphylococcus aureus. Biol. Pharm. Bull., 1997, 20(4), 401-404.
[http://dx.doi.org/10.1248/bpb.20.401 ] [PMID: 9145218]
[55]
Bussi, G.; Donadio, D.; Parrinello, M. Canonical sampling through velocity rescaling. J. Chem. Phys., 2007, 126(1)014101
[http://dx.doi.org/10.1063/1.2408420 ] [PMID: 17212484]
[56]
Schulz, C.; Schütte, K.; Malfertheiner, P. Does H. pylori eradication therapy benefit patients with hepatic encephalopathy?: systematic review. J. Clin. Gastroenterol., 2014, 48(6), 491-499.
[http://dx.doi.org/10.1097/MCG.0000000000000108 ] [PMID: 24583758]
[57]
Babu, T.M.C.; Rajesh, S.S.; Bhaskar, B.V.; Devi, S.; Rammohan, A.; Sivaraman, T.; Rajendra, W. Molecular docking, molecular dynamics simulation, biological evaluation and 2D QSAR analysis of flavonoids from Syzygium alternifolium as potent anti-Helicobacter pylori agents. RSC Advances, 2017, 7, 18277-18292.
[http://dx.doi.org/10.1039/C6RA27872H]
[58]
El-Tawil, O.; Moussa, S.Z. Antioxidant and hepatoprotective effects of thymoquinone against carbon tetrachloride-induced hepatotoxicity in isolated rat hepatocyte. J. Egypt. Soc. Toxicol., 2006, 34, 33-41.
[59]
Toppozada, H.H.; Mazloum, H.A.; el-Dakhakhny, M. The antibacterial properties of the Nigella sativa L. seeds. Active principle with some clinical applications. J. Egypt. Med. Assoc., 1965, 48, 187-202.
[PMID: 5873673]
[60]
O’Mahony, R.; Al-Khtheeri, H.; Weerasekera, D.; Fernando, N.; Vaira, D.; Holton, J.; Basset, C. Bactericidal and anti-adhesive properties of culinary and medicinal plants against Helicobacter pylori. World J. Gastroenterol., 2005, 11(47), 7499-7507.
[http://dx.doi.org/10.3748/wjg.v11.i47.7499 ] [PMID: 16437723]
[61]
Biglar, M.; Sufi, H.; Bagherzadeh, K.; Amanlou, M.; Mojab, F. Screening of 20 commonly used Iranian traditional medicinal plants against urease. Iran. J. Pharm. Res., 2014, 13(Suppl.), 195-198.
[PMID: 24711846]
[62]
Salem, E.M.; Yar, T.; Bamosa, A.O.; Al-Quorain, A.; Yasawy, M.I.; Alsulaiman, R.M.; Randhawa, M.A. Comparative study of Nigella sativa and triple therapy in eradication of Helicobacter Pylori in patients with non-ulcer dyspepsia. Saudi J. Gastroenterol., 2010, 16(3), 207-214.
[http://dx.doi.org/10.4103/1319-3767.65201 ] [PMID: 20616418]
[63]
Biglar, M.; Sufi, H.; Bagherzadeh, K.; Amanlou, M.; Mojab, F. Screening of 20 commonly used Iranian traditional medicinal plants against urease. Iran. J. Pharm. Res., 2014, 13(Suppl.), 195-198.
[PMID: 24711846]
[64]
Atapour, M.; Zahedi, M.J.; Mehrabani, M.; Safavi, M.; Keyvanfard, V.; Foroughi, A. In vitro susceptibility of the Gram-negative bacterium Helicobacter pylori to extracts of Iranian medicinal plants. Pharm. Biol., 2009, 49, 77-80.
[http://dx.doi.org/10.1080/13880200802434401]
[65]
Suzuki, S.; Esaki, M.; Kusano, C.; Ikehara, H.; Gotoda, T. Development of Helicobacter pylori treatment: How do we manage antimicrobial resistance? World J. Gastroenterol., 2019, 25(16), 1907-1912.
[http://dx.doi.org/10.3748/wjg.v25.i16.1907 ] [PMID: 31086459]
[66]
Bukhari, M.H.; Khalil, J.; Qamar, S.; Qamar, Z.; Zahid, M.; Ansari, N.; Bakhshi, I.M. Comparative gastroprotective effects of natural honey, Nigella sativa and cimetidine against acetylsalicylic acid induced gastric ulcer in albino rats. J. Coll. Physicians Surg. Pak., 2011, 21(3), 151-156.
[PMID: 21419021]
[67]
Longo, D.; Fauc, A.; Kasper, D.; Hauser, S.; Jameson, J.; Loscalzo, J. Harrison’s Principles of Internal Medicine, 18th ed; Mc GrawHill: USA, 2012, pp. 1261-125.
[68]
Khaleghi, S.; Taher, M.T.; Naghibi, S.S.; Naghibi, S.M. Comparison of sequential and routine four drugs therapeutic regiments in Helicobacter pylori eradication. J. Gorgan Uni. Med. Sci., 2013.p 15.
[69]
Magdy, M.A.; Hanan, A.; Nabila, M. Thymoquinone: Novel gastroprotective mechanisms. Eur. J. Pharmacol., 2012, 697(1-3), 126-131.
[http://dx.doi.org/10.1016/j.ejphar.2012.09.042 ] [PMID: 23051678]
[70]
Ahmad, A.; Husain, A.; Mujeeb, M. Khan. S.A.; Najmi, A.K.; Siddique, N.A. A review on therapeutic potential of Nigella sativa: A miracle herb. Asian Pac. J. Trop. Biomed., 2013, 3, 337-352.
[http://dx.doi.org/10.3390/molecules20010929]
[71]
Hashem-Dabaghian, F.; Agah, S.; Taghavi-Shirazi, M.; Ghobadi, A. Combination of Nigella sativa and honey in eradication of gastric Helicobacter pylori infection. Iran. Red Crescent Med. J., 2016, 18(11)e23771
[http://dx.doi.org/10.5812/ircmj.23771 ] [PMID: 28191328]
[72]
Chou, K.C. Structural bioinformatics and its impact to biomedical science. Curr. Med. Chem., 2004, 11(16), 2105-2134.
[http://dx.doi.org/10.2174/0929867043364667 ] [PMID: 15279552]
[73]
Chou, K.C.; Watenpaugh, K.D.; Heinrikson, R.L. A model of the complex between cyclin-dependent kinase 5 and the activation domain of neuronal Cdk5 activator. Biochem. Biophys. Res. Commun., 1999, 259(2), 420-428.
[http://dx.doi.org/10.1006/bbrc.1999.0792 ] [PMID: 10362524]
[74]
Zhang, J.; Luan, C.H.; Chou, K.C.; Johnson, G.V. Identification of the N-terminal functional domains of Cdk5 by molecular truncation and computer modeling. Proteins, 2002, 48(3), 447-453.
[http://dx.doi.org/10.1002/prot.10173 ] [PMID: 12112670]
[75]
Wang, J.F.; Chou, K.C. Insights into the mutation-induced HHH syndrome from modeling human mitochondrial ornithine transporter-1. PLoS One, 2012, 7(1)e31048
[http://dx.doi.org/10.1371/journal.pone.0031048 ] [PMID: 22292090]
[76]
Chou, K.C.; Li, T.T.; Forsén, S. The critical spherical shell in enzymatic fast reaction systems. Biophys. Chem., 1980, 12(3-4), 265-269.
[http://dx.doi.org/10.1016/0301-4622(80)80003-2 ] [PMID: 7225519]
[77]
Chou, K.C.; Forsen, S. Graphical rules of steady-state reaction systems. Can. J. Chem., 1981, 59, 737-755.
[http://dx.doi.org/10.1139/v81-107]
[78]
Chou, K.C.; Jiang, S.P.; Liu, W.M.; Fee, C.H. Graph theory of enzyme kinetics: 1. Steady-state reaction system. Sci. Sin., 1979, 22, 341-358.
[79]
Zhou, G.P. The disposition of the LZCC protein residues in wenxiang diagram provides new insights into the protein-protein interaction mechanism. J. Theor. Biol., 2011, 284(1), 142-148.
[http://dx.doi.org/10.1016/j.jtbi.2011.06.006 ] [PMID: 21718705]
[80]
Jia, J.; Liu, Z.; Xiao, X.; Liu, B.; Chou, K.C. Identification of protein-protein binding sites by incorporating the physicochemical properties and stationary wavelet transforms into pseudo amino acid composition. J. Biomol. Struct. Dyn., 2016, 34(9), 1946-1961.
[http://dx.doi.org/10.1080/07391102.2015.1095116 ] [PMID: 26375780]
[81]
Chou, K.C.; Shen, H.B. Recent advances in developing web-servers for predicting protein attributes. Nat. Sci., 2009, 1, 63-92.
[http://dx.doi.org/10.4236/ns.2009.12011]
[82]
Chou, K.C.; Cheng, X.; Xiao, X. pLoc_bal-mEuk: predict subcellular localization of eukaryotic proteins by general PseAAC and quasi-balancing training dataset. Med. Chem., 2019, 15(5), 472-485.
[http://dx.doi.org/10.2174/1573406415666181218102517 ] [PMID: 30569871]
[83]
Xiao, X.; Cheng, X.; Chen, G.; Mao, Q.; Chou, K.C. pLoc_bal-mVirus: predict subcellular localization of multi-label virus proteins by PseAAC and IHTS treatment to balance training dataset. Med. Chem., 2019, 15(5), 496-509.
[http://dx.doi.org/10.2174/1573406415666181217114710 ] [PMID: 30556503]
[84]
Chou, K.C. An unprecedented revolution in medicinal chemistry driven by the progress of biological science. Curr. Top. Med. Chem., 2017, 17(21), 2337-2358.
[http://dx.doi.org/10.2174/1568026617666170414145508 ] [PMID: 28413951]
[85]
Chou, K.C. Advance in predicting subcellular localization of multi-label proteins and its implication for developing multi-target drugs. Curr. Med. Chem., 2019. [Online ahead of print
[http://dx.doi.org/10.2174/0929867326666190507082559 ] [PMID: 31060481]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 17
ISSUE: 2
Year: 2021
Published on: 01 March, 2020
Page: [146 - 157]
Pages: 12
DOI: 10.2174/1573406416666200302113729
Price: $65

Article Metrics

PDF: 24
HTML: 1