ADMETox-informatics of Plant Derived Octadecanoic Acid (Stearic Acid) from Ethyl Acetate Fraction of Moringa oleifera Leaf Extract as a Natural Lead for Next Generation Drug Design, Development and Therapeutics
In-silico Computer-Aided Drug Design (CADD) significantly relies on cybernetic screening of Plant Based Natural Products (PBNPs) as a prime source of bioactive compounds/ drug leads due to their unique chemical structural scaffolds and distinct functional characteristic features amenable to drug design and development. In the Post-COVID-Era a large number of publications have focused on PBNPs. Moreover, PBNPs still remain as an ideal source of novel therapeutic agents of GRAS standard. However, a well-structured, in-depth ADME/Tox profile with deeper dimensions of PBNPs has been lacking for many of natural pharma lead molecules that hamper successful exploitation of PBNPs. In the present study, ADMET-informatics of Octadecanoic Acid (Stearic Acid - SA) from ethyl acetate fraction of Moringa oleifera leaves has been envisaged to predict ADMET and pharmacokinetics (DMPK) outcomes. This work contributes to the deeper understanding of SA as major source of drug lead from Moringa oleifera with immense therapeutic potential. The data generated herein could be useful for the development of SA as plant based natural product lead (PBNPL) for drug development programs.
Keywords: Moringa oleifera; Bioactive Substances; Octadecanoic Acid; Stearic Acid; ADME/Tox; Natural Product Based Drug Lead; PBNPs
2. Meyer F, Bloch K. Metabolism of stearolic acid in yeast. Journal of Biological Chemistry. 1963 Aug 1; 238(8):2654-9. https://doi.org/10.1016/S0021-9258(18)67881-0
3. Warra AA, Jonathan BL, Ibrahim BD, Adedara AO. GC-MS Analysis of Hexane Extracts of Two Varieties of Sesame (Sesamun indicum L.) Seed Oil. IJCPT 2016; 1(1):1-9
4. Dollah S, Abdulkarim SM, Ahmad SH, Khoramnia A, Mohd Ghazali H. Physico‐chemical properties of Moringa oleifera seed oil enzymatically inter-esterified with palm stearin and palm kernel oil and its potential application in food. Journal of the Science of Food and Agriculture. 2016 Aug; 96(10):3321-33. https://doi.org/10.1002/jsfa.7510
5. Ramya S, Neethirajan K, Jayakumararaj R. Profile of bioactive compounds in Syzygium cumini-a review. Journal of Pharmacy Research. 2012; 5(8):4548-53.
6. Kandeepan C, Suganandam K, Jeevalatha A, Kavitha N, Senthilkumar N, Sutha S, Syed MA, Gandhi S, Ramya S, Grace Lydial Pushpalatha G, Abraham GC, King Immanuel J, Jayakumararaj R, ADMETE valuation, Pharmacokinetics, Drug-likeness and Medicinal Chemistry of GCMS Identified Bioactive Compounds of Moringa oleifera Natural-Ripened Dried Methanolic Pod Extract (MOMPE) as a Potential Source of Natural Drug Frontrunner for Next Generation Drug Design, Development and Therapeutics, Journal of Drug Delivery and Therapeutics. 2022; 12(6):65-85 https://doi.org/10.22270/jddt.v12i5-S.5657
7. Ramya S., Chandran M., King IJ., Jayakumararaj R., Loganathan T., Pandiarajan G., Kaliraj P., Grace Lydial Pushpalatha G, Abraham GC., Vijaya V., Aruna D, Sutha S, Dhakar RC, Phytochemical Screening, GCMS and FTIR Profile of Bioactive Compounds in Solanum lycopersicum Wild Fruits collected from Palani Hill Ranges of the Western Ghats, Journal of Drug Delivery and Therapeutics. 2022; 12(6):56-64 https://doi.org/10.22270/jddt.v12i2-S.5280
8. Chandran M, Priyanka R, Kavipriya D, Ramya S, Jayakumararaj R, Loganathan T, Pandiarajan G, Kaliraj P, Pushpalatha GG, Abraham GC, Dhakar RC. Reformulation and Scientific Evaluation of CUSOCO: A Traditional Toothpaste Formula from Classical Tamil Literature towards treatment of Halitosis. Journal of Drug Delivery and Therapeutics. 2022; 12(5):127-31. https://doi.org/10.22270/jddt.v12i5.5604
9. Kalaimathi RV, Krishnaveni K, Murugan M, Basha AN, Gilles AP, Kandeepan C, Senthilkumar N, Mathialagan B, Ramya S, Ramanathan L, Jayakumararaj R. ADMET informatics of Tetradecanoic acid (Myristic Acid) from ethyl acetate fraction of Moringa oleifera leaves. Journal of Drug Delivery and Therapeutics. 2022; 12(4-S):101-11. https://doi.org/10.22270/jddt.v12i4-S.5533
10. Nazar S, Jeyaseelan M, Jayakumararaj R. Local Health Traditions, Cultural Reflections and Ethno-taxonomical Information on Wild Edible Fruit Yielding Medicinal Plants in Melur Region of Madurai District, TamilNadu, India. Journal of Drug Delivery and Therapeutics. 2022; 12(3):138-57. https://doi.org/10.22270/jddt.v12i3.5405
11. Murugan M, Krishnaveni K, Sabitha M, Kandeepan C, Senthilkumar N, Loganathan T, Pushpalatha GL, Pandiarajan G, Ramya S, Jayakumararaj R. In silico Target Class Prediction and Probabilities for Plant Derived Omega 3 Fatty Acid from Ethyl Acetate Fraction of Moringa oleifera Leaf Extract. Journal of Drug Delivery and Therapeutics. 2022; 12(3):124-37. https://doi.org/10.22270/jddt.v12i3.5352
12. Parvathi K, Kandeepan C, Sabitha M, Senthilkumar N, Ramya S, Boopathi NM, Ramanathan L, Jayakumararaj R. In-silico Absorption, Distribution, Metabolism, Elimination and Toxicity profile of 9, 12, 15-Octadecatrienoic acid (ODA) from Moringa oleifera. Journal of Drug Delivery and Therapeutics. 2022; 12(2-S):142-50. https://doi.org/10.22270/jddt.v12i2-S.5289
13. Ramya S, Loganathan T, Chandran M, Priyanka R, Kavipriya K, Pushpalatha GG, Aruna D, Ramanathan L, Jayakumararaj R, Saluja V. Phytochemical Screening, GCMS, FTIR profile of Bioactive Natural Products in the methanolic extracts of Cuminum cyminum seeds and oil. Journal of Drug Delivery and Therapeutics. 2022; 12(2-S):110-8. https://doi.org/10.22270/jddt.v12i2-S.5280
14. Kandeepan C, Sabitha M, Parvathi K, Senthilkumar N, Ramya S, Boopathi NM, Jayakumararaj R. Phytochemical Screening, GCMS Profile, and In-silico properties of Bioactive Compounds in Methanolic Leaf Extracts of Moringa oleifera. Journal of Drug Delivery and Therapeutics. 2022; 12(2):87-99. https://doi.org/10.22270/jddt.v12i2.5250
15. Krishnaveni K, Sabitha M, Murugan M, Kandeepan C, Ramya S, Loganathan T, Jayakumararaj R. vNN model cross validation towards Accuracy, Sensitivity, Specificity and kappa performance measures of β-caryophyllene using a restricted-unrestricted applicability domain on Artificial Intelligence & Machine Learning approach based in-silico prediction. Journal of Drug Delivery and Therapeutics. 2022; 12(1-S):123-31. https://doi.org/10.22270/jddt.v12i1-S.5222
16. Jeevalatha A, Kalaimathi RV, Basha AN, Kandeepan C, Ramya S, Loganathan T, Jayakumararaj R. Profile of bioactive compounds in Rosmarinus officinalis. Journal of Drug Delivery and Therapeutics. 2022; 12(1):114-22. https://doi.org/10.22270/jddt.v12i1.5189
17. Kalaimathi RV, Jeevalatha A, Basha AN, Kandeepan C, Ramya S, Loganathan T, Jayakumararaj R. In-silico Absorption, Distribution, Metabolism, Elimination and Toxicity profile of Isopulegol from Rosmarinus officinalis. Journal of Drug Delivery and Therapeutics. 2022; 12(1):102-8. https://doi.org/10.22270/jddt.v12i1.5188
18. Ramya S, Loganathan T, Chandran M, Priyanka R, Kavipriya K, Pushpalatha GL, Aruna D, Abraham GC, Jayakumararaj R. ADME-Tox profile of Cuminaldehyde (4-Isopropylbenzaldehyde) from Cuminum cyminum seeds for potential biomedical applications. Journal of Drug Delivery and Therapeutics. 2022; 12(2-S):127-41. https://doi.org/10.22270/jddt.v12i2-S.5286
19. Ramya S, Murugan M, Krishnaveni K, Sabitha M, Kandeepan C, Jayakumararaj R. In-silico ADMET profile of Ellagic Acid from Syzygium cumini: A Natural Biaryl Polyphenol with Therapeutic Potential to Overcome Diabetic Associated Vascular Complications. Journal of Drug Delivery and Therapeutics. 2022; 12(1):91-101. https://doi.org/10.22270/jddt.v12i1.5179
20. Ramya S, Soorya C, Pushpalatha GG, Aruna D, Loganathan T, Balamurugan S, Abraham GC, Ponrathy T, Kandeepan C, Jayakumararaj R. Artificial Intelligence and Machine Learning approach based in-silico ADME-Tox and Pharmacokinetic Profile of α-Linolenic acid from Catharanthus roseus (L.) G. Don. Journal of Drug Delivery and Therapeutics. 2022; 12(2-S):96-109. https://doi.org/10.22270/jddt.v12i2-S.5274
21. Ramya S, Sutha S, Chandran M. Priyanka R, Loganathan T, Pandiarajan G, Kaliraj P, Grace Lydial Pushpalatha G, Abraham GC Jayakumararaj R, ADMET-informatics, Pharmacokinetics, Drug-likeness and Medicinal Chemistry of Bioactive Compounds of Physalis minima Ethanolic Leaf Extract (PMELE) as a Potential Source of Natural Lead Molecules for Next Generation Drug Design, Development and Therapies , Journal of Drug Delivery and Therapeutics. 2022; 12(5):188-200 https://doi.org/10.22270/jddt.v12i5.5654
22. Suganandam K, Jeevalatha A, Kandeepan C, Kavitha N, Senthilkumar N, Sutha S, Syed MA, Gandhi S, Ramya S, Grace Lydial Pushpalatha G, Abraham GC, Jayakumararaj R, Profile of Phytochemicals and GCMS Analysis of Bioactive Compounds in Natural Dried-Seed Removed Ripened Pods Methanolic Extracts of Moringa oleifera, Journal of Drug Delivery and Therapeutics. 2022; 12(5-S):133-141 https://doi.org/10.22270/jddt.v12i5-S.5657
23. Kandeepan C, Kalaimathi RV, Jeevalatha A, Basha AN, Ramya S, Jayakumararaj R. In-silico ADMET Pharmacoinformatics of Geraniol (3, 7-dimethylocta-trans-2, 6-dien-1-ol)-acyclic monoterpene alcohol drug from Leaf Essential Oil of Cymbopogon martinii from Sirumalai Hills (Eastern Ghats), INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4-S):109-18. https://doi.org/10.22270/jddt.v11i4-S.4965
24. Loganathan T, Barathinivas A, Soorya C, Balamurugan S, Nagajothi TG, Ramya S, Jayakumararaj R. Physicochemical, Druggable, ADMET Pharmacoinformatics and Therapeutic Potentials of Azadirachtin-a Prenol Lipid (Triterpenoid) from Seed Oil Extracts of Azadirachta indica A. Juss. Journal of Drug Delivery and Therapeutics. 2021; 11(5):33-46. https://doi.org/10.22270/jddt.v11i5.4981
25. Sabitha M, Krishnaveni K, Murugan M, Basha AN, Pallan GA, Kandeepan C, Ramya S, Jayakumararaj R. In-silico ADMET predicated Pharmacoinformatics of Quercetin-3-Galactoside, polyphenolic compound from Azadirachta indica, a sacred tree from Hill Temple in Alagarkovil Reserve Forest, Eastern Ghats, INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(5-S):77-84. https://doi.org/10.22270/jddt.v11i5-S.5026
26. Soorya C, Balamurugan S, Basha AN, Kandeepan C, Ramya S, Jayakumararaj R. Profile of Bioactive Phyto-compounds in Essential Oil of Cymbopogon martinii from Palani Hills, Western Ghats, INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4):60-5. https://doi.org/10.22270/jddt.v11i4.4887
27. Soorya C, Balamurugan S, Ramya S, Neethirajan K, Kandeepan C, Jayakumararaj R. Physicochemical, ADMET and Druggable properties of Myricetin: A Key Flavonoid in Syzygium cumini that regulates metabolic inflammations. Journal of Drug Delivery and Therapeutics. 2021; 11(4):66-73. https://doi.org/10.22270/jddt.v11i4.4890
28. Shanmugam S, Sundari A, Muneeswaran S, Vasanth C, Jayakumararaj R, Rajendran K. Ethnobotanical Indices on medicinal plants used to treat poisonous bites in Thiruppuvanam region of Sivagangai district in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(6-s):31-6. https://doi.org/10.22270/jddt.v10i6-s.4432
29. Sundari A, Jayakumararaj R. Herbal remedies used to treat skin disorders in Arasankulam region of Thoothukudi District in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(5):33-8. https://doi.org/10.22270/jddt.v10i5.4277
30. Sundari A, Jayakumararaj R. Medicinal plants used to cure cuts and wounds in Athur region of Thoothukudi district in Tamil Nadu, India. Journal of Drug Delivery and Therapeutics. 2020; 10(6-s):26-30. https://doi.org/10.22270/jddt.v10i6-s.4429
31. Meena R, Prajapati SK, Nagar R, Porwal O, Nagar T, Tilak VK, Jayakumararaj R, Arya RK, Dhakar RC. Application of Moringa oleifera in Dentistry. Asian Journal of Dental and Health Sciences. 2021; 1(1):10-3. https://doi.org/10.22270/ijmspr.v6i1.25
32. Beetge E, du Plessis J, Müller DG, Goosen C, van Rensburg FJ. The influence of the physicochemical characteristics and pharmacokinetic properties of selected NSAID's on their transdermal absorption. International journal of Pharmaceutics. 2000; 193(2):261-4. https://doi.org/10.1016/S0378-5173(99)00340-3
33. Mabkhot YN, Alatibi F, El-Sayed NN, Al-Showiman S, Kheder NA, Wadood A, Rauf A, Bawazeer S, Hadda TB. Antimicrobial activity of some novel armed thiophene derivatives and petra/osiris/molinspiration (POM) analyses. Molecules. 2016; 21(2):222. https://doi.org/10.3390/molecules21020222
34. Hauser AS, Attwood MM, Rask-Andersen M, Schiöth HB, Gloriam DE. Trends in GPCR drug discovery: new agents, targets and indications. Nature reviews Drug discovery. 2017 Dec; 16(12):829-42. https://doi.org/10.1038/nrd.2017.178
35. Daina A, Michielin O, Zoete V. SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific reports. 2017; 7(1):1-3 https://doi.org/10.1038/srep42717
36. Hubatsch I, Ragnarsson EG, Artursson P. Determination of drug permeability and prediction of drug absorption in Caco-2 monolayers. Nature protocols. 2007; 2(9):2111-9. https://doi.org/10.1038/nprot.2007.303
37. Radchenko EV, Dyabina AS, Palyulin VA, Zefirov NS. Prediction of human intestinal absorption of drug compounds. Russian Chemical Bulletin. 2016; 65(2):576-80. https://doi.org/10.1007/s11172-016-1340-0
38. Alam A, Kowal J, Broude E, Roninson I, Locher KP. Structural insight into substrate and inhibitor discrimination by human Pglycoprotein. Science. 2019; 363(6428):753-6. https://doi.org/10.1126/science.aav7102
39. Daina A, Zoete V. A boiled‐egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem. 2016; 11(11):1117-21. https://doi.org/10.1002/cmdc.201600182
40. Liao M, Jaw-Tsai S, Beltman J, Simmons AD, Harding TC, Xiao JJ. Evaluation of in vitro absorption, distribution, metabolism, and excretion and assessment of drug-drug interaction of rucaparib, an orally potent poly (ADP-ribose) polymerase inhibitor. Xenobiotica. 2020; 50(9):1032-42. https://doi.org/10.1080/00498254.2020.1737759
41. Jia CY, Li JY, Hao GF, Yang GF. A drug-likeness toolbox facilitates ADMET study in drug discovery. Drug Discovery Today. 2020; 25(1):248-58. https://doi.org/10.1016/j.drudis.2019.10.014
42. Cheng F, Li W, Zhou Y, Shen J, Wu Z, Liu G, Lee PW, Tang Y. admetSAR: a comprehensive source and free tool for assessment of chemical ADMET properties.
43. Schyman, P., R. Liu, V. Desai, and A. Wallqvist. vNN web server for ADMET predictions. Frontiers in Pharmacology. 2017 December 4; 8:889. https://doi.org/10.3389/fphar.2017.00889
44. Liu, R., P. Schyman, and A. Wallqvist. Critically assessing the predictive power of QSAR models for human liver microsomal stability. Journal of Chemical Information and Modeling. 2015; 55(8):1566-1575. https://doi.org/10.1021/acs.jcim.5b00255
45. Xu, Y., Z. Dai, F. Chen, S. Gao, J. Pei, and L. Lai. Deep learning for drug induced liver injury. 2015, 55(10):2085-2093. https://doi.org/10.1021/acs.jcim.5b00238
46. Muehlbacher, M., G. Spitzer, K. Liedl, J. Kornhuber. Qualitative prediction of blood-brain barrier permeability on a large and refined dataset. Journal of Computer-Aided Molecular Design. 2011; 25:1095. https://doi.org/10.1007/s10822-011-9478-1
47. Schyman, P., R. Liu, and A. Wallqvist. Using the variable-nearest neighbor method to identify P-glycoprotein substrates and inhibitors. ACS Omega. 2016; 1(5):923-929 https://doi.org/10.1021/acsomega.6b00247
48. Schyman, P., R. Liu, and A. Wallqvist. General purpose 2D and 3D similarity approach to identify hERG blockers. Journal of Chemical Information and Modeling. 2016; 56(1):213-222 https://doi.org/10.1021/acs.jcim.5b00616
49. Liu, R., G. Tawa, and A. Wallqvist. Locally weighted learning methods for predicting dose-dependent toxicity with application to the human maximum recommended daily dose. Chemical Research in Toxicology. 2012; 25(10):2216-2226. https://doi.org/10.1021/tx300279f
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).