Molecular basis of some antimicrobial potential compounds from Mitragyna inermis (Willd.) O. Ktze dichloromethane fraction
DOI:
https://doi.org/10.64707/revstss.v48i2.1833Keywords:
Mitragyna inermis, non-polar compounds, antimicrobial, dichloromethane fraction, virtual screeningAbstract
Virtual screening has become a modern diagnostic tool upstream of experimental laboratory tests for discovering hit molecules. This screening estimates the affinitý and plausible binding mode of potential active ingredients to therapeutic targets. To this end, the dichloromethane fraction of Mitragyna inermis (Willd.) O. Ktze trunk bark is potentially active on microorganisms, but the nature of the compounds as well as their involvement as active ingredients remains unknown. To this end, thin-layer chromatographic analysis, nuclear magnetic resonance analysis, gageous phase chromatography and mass spectrometry were carried out on this fraction. Then, a virtual screening with AutoDock Vina waś performed on various targets of antimicrobial mechanisms such as, microbial urease, dihydroteroate synthetase, 14-α-demethylase, squalene epoxidase, Sap1 aspartic proteinase, quorum sensing signal receptor LasR, topoisomerase II DNA gyrase, tyrosyl-tRNA synthetase and beta-lactamase. Following these analyses, the pharmacokinetic profile of the identified compounds defined with SwissADME was used to filter out potential drugs. From these analyses, fourteen more or less apolar compounds weré identified. Two of these, 6-((2-ethylhexyl)oxy)-6-oxohexanoic acid and 2-((2-ethylhexyl)oxy)carbonyl)benzoic acid, proved to be hit molecules. As a result, further studies can be undertaken for in vitro validation as potential antimicrobials.
References
(1) ARBONNIER M. Arbres, Arbustes et Lianes Des Zones Sèches d’Afrique de l’Ouest. Edited by Pont- sur-Yvonne Artecom. Cirad. 2002 ; 87p.
(2) ZERBO P, MILLOGO-RASOLODIMEY J, NACOULMA-OUEDRAOGO OG, VAN DAMME P. Contribution à la connaissance des plantes médicinales utilisées dans les soins infantiles en pays San, au Burkina Faso. Int J Biol Chem Sci. 2007 ; 1(3):262-274. doi:10.4314/ijbcs.v1i3.39704
(3) ASASE A, KOKUBUN T, GRAYER RJ, KITE G, SIMMONDS MS, OTENG‐YEBOAH AA et al. Chemical constituents and antimicrobial activity of medicinal plants from Ghana: Cassia sieberiana, Haematostaphis barteri, Mitragyna inermis and Pseudocedrela kotschyi. Phytother Res. 2008; 22(8):1013-1016. https://doi.org/10.1002/ptr.2392
(4) ADOUM OA, NENGE HP, CHEDI B. The steroidal component and hypoglycaemic effect of stem bark extract of Mitragyna inermis (wild) O. Kundze (Rubiaceae) in alloxan induced diabetic wistar rats. Int J Appl Biol Pharm. 2012; 3:169–74.
(5) DONFACK EV, LENTA BN, KONGUE MDT, FONGANG YF, NGOUELA S, TSAMO E et al. Naucleactonin D, an indole alkaloid and other chemical constituents from roots and fruits of Mitragyna inermis. Z. Naturforsch., B: Chem. Sci. 2012; 67(11):1159-1165. https://doi.org/10.5560/znb.2012-0115
(6) MUKHTAR M, ADAMU HM, FALALU MY. GC-MS analysis and identification of constituents present in the root extract of Mitragyna inermis. J Pharmacogn Phytochem. 2016; 5 (6):17-20.
(7) POLITEO O, JUKIC M, MILOS M. Chemical composition and antioxidant capacity of free volatile aglycones from basil (Ocimum basilicum L.) compared with its essential oil. Food Chem. 2007; 101(1):379-385. https://doi.org/10.1016/j.foodchem.2006.01.045
(8) HSIEH TJ, TSAI YH, LIAO MC, DU YC, LIEN PJ, SUN CC et al. Anti-diabetic properties of non-polar Toona sinensis Roem extract prepared by supercritical-CO2 fluid. Food Chem Toxicol. 2012; 50(3-4):779-789. https://doi.org/10.1016/j.fct.2011.12.023
(9) FOMANI M, NOUGA AB, TOZE FAA, NDOM JC, WAFFO AFK, WANSI JD. Bioactive Phenylethanoids from the Seeds of Manilkara zapota. J Pharm Res Int. 2015; 8(5):1-5. doi: 10.9734/BJPR/2015/20796
(10) SHARMA N, GUPTA N, ORFALI R, KUMAR V, PATEL CN, PENG J et al. Evaluation of the Antifungal, Antioxidant, and Anti-Diabetic Potential of the Essential Oil of Curcuma longa Leaves from the North-Western Himalayas by In Vitro and In Silico Analysis. Molecules. 2022; 27(22):7664. https://doi.org/10.3390/molecules27227664
(11) OUÉDRAOGO RJ, OUATTARA L, KABRE P, SANOU Y, SOMDA MB, OUOBA P et al. Season and Ecotype Effects on Soluble Phenolic Compounds Content and Antioxidant Potential of Tamarindus indica and Mitragyna inermis. J Pharm Pharmacol. 2022; 10(5):145-158. doi: 10.17265/2328-2150/2022.05.001
(12) OUÉDRAOGO RJ, JAMAL M, OUATTARA L, NADEEM-UL-HAQUE M, KHAN F, SIMJEE SU et al. Antiseizure Activity of Mitragyna inermis in the Pentylenetetrazol-Induced Seizure Model in Mice: Involvement of Flavonoids and Alkaloids. Turkish Journal of Pharmaceutical Sciences. 2024; 21(2), 104-112. doi: 10.4274/tjps.galenos.2023.14704
(13) TROTT O, OLSON AJ. AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization and multithreading, Journal of Computational Chemistry. 2010; 31(2): 455-461. https://doi.org/10.1002/jcc.21334
(14) HA NC, OH ST, SUNG JY, CHA KA, LEE MH, OH BH. Supramolecular assembly and acid resistance of Helicobacter pylori urease. Nat Struct Biol. 2001; 8(6):505-509. https://doi.org/10.1038/88563
(15) FRIGGERI L, HARGROVE TY, WAWRZAK Z, BLOBAUM AL, RACHAKONDA G, LINDSLEY CW et al. Sterol 14-α-Demethylase Structure-Based Design of VNI (( R)- N-(1-(2,4-Dichlorophenyl)-2-(1 H-imidazol-1-yl)ethyl)-4-(5-phenyl-1,3,4-oxadiazol-2-yl)benzamide)) Derivatives To Target Fungal Infections: Synthesis, Biological Evaluation, and Crystallographic Analysis. J Med Chem. 2018; 61(13):5679-5691. https://doi.org/10.1021/acs.jmedchem.8b00641
(16) QIU X, JANSON CA, SMITH WW, GREEN SM, MCDEVITT P, JOHANSON K et al. Crystal structure of Staphylococcus aureus tyrosyl-tRNA synthetase in complex with a class of potent and specific inhibitors. Protein Sci. 2001; 10(10):2008-2016. https://doi.org/10.1110/ps.18001
(17) BAX BD, CHAN PF, EGGLESTON DS, FOSBERRY A, GENTRY DR, GORREC F et al. Type IIA topoisomerase inhibition by a new class of antibacterial agents. Nature. 2010; 466(7309):935-940. https://doi.org/10.1038/nature09197
(18) PADYANA AK, GROSS S, JIN L, CIANCHETTA G, NARAYANASWAMY R, WANG F et al. Structure and inhibition mechanism of the catalytic domain of human squalene epoxidase. Nat Commun. 2019; 10(97):1-10. https://doi.org/10.1038/s41467-018-07928-x
(19) CHEN CC, RAHIL J, PRATT RF, HERZBERG O. Structure of a phosphonate-inhibited beta-lactamase. An analog of the tetrahedral transition state/intermediate of beta-lactam hydrolysis. J Mol Biol. 1993; 234(1):165-178. https://doi.org/10.1006/jmbi.1993.1571
(20) PHILIPP S, SARAH NB, KATJA L, MICHAEL S. PLIP 2025: introducing protein-protein interactions to the protein-ligand interaction profiler, Nucleic Acids Research. 2025; 53 (W1):W463-W465. https://doi.org/10.1093/nar/gkaf361
(21) DAINA A, MICHIELIN O, ZOETE V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Sci Rep. 2016; 7(1):1-13. https://doi.org/10.1038/srep42717
(22) FRANCIS F, KING AM, WILLIS JA. Long-chain carbon compounds. n-Tetratriacontanoic and n-hexatetracontanoic acids and their derivatives. J Chem Soc (Resumed). 1937; 210:999-1004. https://doi.org/10.1039/JR9370000999
(23) GOLOVNYA RV, URALETS VP, KUZMENKO TE. Characterization of fatty acid methyl esters by gas chromatography on siloxane liquid phases. J Chromatogr A. 1976; 121:118-121. doi: 10.1016/S0021-9673(00)82312-2
(24) PENG CT. Prediction of retention indices: V. Influence of electronic effects and column polarity on retention index. J Chromatogr A. 2000; 903(1-2):117-143. https://doi.org/10.1016/S0021-9673(00)00901-8
(25) PINO JA, MARBOT R. Volatile flavor constituents of acerola (Malpighia emarginata DC.) fruit. J Agric Food Chem. 2001; 49(12):5880-5882. https://doi.org/10.1021/jf010270g
(26) BLAGOJEVIĆ P, RADULOVIĆ N, PALIĆ R, STOJANOVIĆ G. Chemical composition of the essential oils of Serbian wild-growing Artemisia absinthium and Artemisia vulgaris. J Agric Food Chem. 2006; 54(13):4780-4789. https://doi.org/10.1021/jf060123o
(27) RADULOVIĆ N, MANANJARASOA E, HARINANTENAINA L, YOSHINORI A. Essential oil composition of four Croton species from Madagascar and their chemotaxonomy. Biochem Syst Ecol. 2006; 8:648-653. doi: 10.1016/j.bse.2006.02.005
(28) REZAZADEH S, PIRALI HM, HADJIAKHOONDI A, YAZDANI D, JAMSHIDI AH, TAGHIZADEH M. Chemical composition of the essential oils of Stachys athorecalyx C. Koch. collected from Arasbaran prospected region. J Med Plants. 2006; 5(18):56-62.
(29) ZHAO CX, LI XN, LIANG YZ, FANG HZ, HUANG LF, GUO FQ. Comparative analysis of chemical components of essential oils from different samples of Rhododendron with the help of chemometrics methods. Chemometr Intell Lab Syst. 2006; 82(1-2):218-228. https://doi.org/10.1016/j.chemolab.2005.08.008
(30) PAOLINI J, MUSELLI A, BERNARDINI AF, BIGHELLI A, CASANOVA J, COSTA J. Thymol derivatives from essential oil of Doronicum corsicum L. Flavour Fragr J. 2007; 22(6):479-487. https://doi.org/10.1002/ffj.1824
(31) ZENG YX, ZHAO CX, LIANG YZ, YANG H, FANG HZ, YI LZ et al. Comparative analysis of volatile components from Clematis species growing in China. Analytica chimica acta. 2007; 595(1-2):328-339. https://doi.org/10.1016/j.aca.2006.12.022
(32) OUEDRAOGO RJ, AHMAD N, OUATTARA L, UL-HAQ Z, OUEDRAOGO, GA. Mitragyna inermis (Willd.) O. Kuntze ethnopharmacology and metabolic disorders: An update review and in silico study. ACTA Pharmaceutica Sciencia. 2025; 63(1):17-43. doi : 10.23893/1307-2080.APS6302
(33) BOTTOMLEY MJ, MURAGLIA E, BAZZO R, CARFÌ A. Molecular insights into quorum sensing in the human pathogen Pseudomonas aeruginosa from the structure of the virulence regulator LasR bound to its autoinducer. J Biol Chem. 2007; 282(18):13592-600. https://doi.org/10.1074/jbc.M700556200
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