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CC BY 4.0 · Journal of Health and Allied Sciences NU 2024; 14(02): 190-201
DOI: 10.1055/s-0043-1770057
Original Article

In Silico ADMET and Molecular Interaction Profiles of Phytochemicals from Medicinal Plants in Dakshina Kannada

Jainey P. James 
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
,
Puneeth Deepak Ail
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
,
Lenisha Crasta
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
,
Rakshith Sudheer Kamath
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
,
M. H. Shura
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
,
Sindhu T.J
1   Department of Pharmaceutical Chemistry, NGSM Institute of Pharmaceutical Sciences (NGSMIPS), Nitte (deemed to be university), Deralakatte, Mangaluru, Karnataka, India
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Abstract

The success or failure of a potential drug depends on its absorption, distribution, metabolism, excretion and toxicity (ADMET) characteristics, and these features are usually rate-limiting in the drug development process. Hence, it is essential to know about the predicted ADMET properties of the most promising leads to avoid the risk of late-stage attrition. This project focuses on in silico screening of ADMET properties of phytochemicals found in Dakshina Kannada's medicinal plants, which include Tinospora cordifolia, Azadirachta indica, Ocimum sanctum, and Plectranthus amboinicus, mainly known for their antimicrobial properties.

The physicochemical properties, bioactivity scores, ADMET, and molecular interactions of the selected phytoconstituents were determined by QikProp, Molinspiration, ADMETlab 2.0, ProTox-II, and GLIDE. In addition, molecular docking checked for their binding interactions with target proteins 1JIJ and 4 HOE of Staphylococcus aureus and Candida albicans, respectively, as they were well known for their antimicrobial properties. In this studies, rosmarinic acid was well interacted phytochemical with both target proteins and has highest docking score.

The physicochemical properties showed that all compounds fell under the recommended molecular weight, volume, and polar surface area range. Xanosporic acid violated two rules of Lipinski's Rule of Five, indicating that it may have problems with oral bioavailability. The ADME properties for most of the phytocompounds were within the recommended ranges; hence, they are promising candidates for drug development. Most phytoconstituents showed good bioactivity scores, indicating they have good druglikeness properties. On the analysis of the toxicity, most of the phytoconstituents were found to be noncarcinogenic and nonmutagenic. Therefore, this data can further be utilized as primary tools for determining the biological actions of these plants.

Xanosporic acid was found to violate two out of three rules of Lipinski. Similarly, ursolic acid and oleanolic acid also showed a few undesirable properties. All other compounds otherwise showed desirable properties and hence are promising candidates for drug development. This data can be further utilized as primary tool for determining the biological actions of the plants.

Keywords

physicochemical properties - bioactivity scores - ADMET properties - molecular interactions


Publication History

Article published online:
19 June 2023

© 2023. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

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  • References

  • 1 Ntie-Kang F, Lifongo LL, Mbah JA. et al. In silico drug metabolism and pharmacokinetic profiles of natural products from medicinal plants in the Congo basin. In Silico Pharmacol 2013; 1 (01) 12
    CrossrefPubMedGoogle Scholar
  • 2 Darvas F, Keseru G, Papp A, Dormán G, Urge L, Krajcsi P. In silico and Ex silico ADME approaches for drug discovery. Curr Top Med Chem 2002; 2 (12) 1287-1304
    CrossrefPubMedGoogle Scholar
  • 3 Directory of computer-aided Drug Design tools. [Online]. Accessed May 27, 2023 at: https://click2drug.org/directory_ADMET.php
    Google Scholar
  • 4 Salam NK, Adzhigirey M, Sherman W, Pearlman DA. Structure-based approach to the prediction of disulfide bonds in proteins. Protein Eng Des Sel 2014; 27 (10) 365-374
    CrossrefPubMedGoogle Scholar
  • 5 Mishra SS, Kumar N, Singh HP. et al. In silico pharmacokinetic, bioactivity and toxicity study of some selected anti-asthmatic agents. Int J Pharm Sci Drug Res 2018; 10 (04) 278-282
    CrossrefGoogle Scholar
  • 6 Xiong G, Wu Z, Yi J. et al. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. [Online]. 2021 . Accessed May 27, 2023 at: https://admetmesh.scbdd.com/
    PubMedGoogle Scholar
  • 7 ProTox-II. . [Online]. Accessed May 27, 2023 at: https://toxnew.charite.de/protox_II/index.php?site=faq
  • 8 Yi F, Li L, Xu LJ. et al. In silico approach in reveal traditional medicine plants pharmacological material basis. Chin Med 2018; 13 (33) 33
    CrossrefPubMedGoogle Scholar
  • 9 Saha S, Ghosh S. Tinospora cordifolia: one plant, many roles. Anc Sci Life 2012; 31 (04) 151-159
    CrossrefPubMedGoogle Scholar
  • 10 Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment. Evid Based Complement Alternat Med 2016; 2016: 7382506 DOI: 10.1155/2016/7382506.
    CrossrefPubMedGoogle Scholar
  • 11 Cohen MM. Tulsi - Ocimum sanctum: a herb for all reasons. J Ayurveda Integr Med 2014; 5 (04) 251-259
    CrossrefPubMedGoogle Scholar
  • 12 Arumugam G, Swamy MK, Sinniah UR. Plectranthus amboinicus (Lour.) Spreng: botanical, phytochemical, pharmacological and nutritional significance. Molecules 2016; 21 (04) 369
    CrossrefPubMedGoogle Scholar
  • 13 Flora of Peninsular India database. [Online]. Accessed May 27, 2023 at: http://flora-peninsula-indica.ces.iisc.ac.in/index.php
    Google Scholar
  • 14 Upadhyay AK, Kumar K, Kumar A, Mishra HS. Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) - validation of the Ayurvedic pharmacology through experimental and clinical studies. Int J Ayurveda Res 2010; 1 (02) 112-121
    CrossrefPubMedGoogle Scholar
  • 15 Patil RC, Kulkarni CP, Pandey A. Antifungal and phytochemical properties of Tinospora cordifolia, Azadirachta indica and Ocimum sanctum leaves extract. J Med Plants Studies 2017; 5 (05) 23-26
    Google Scholar
  • 16 Sivaranjani D, Saranraj P, Manigandan M, Amala K. Antimicrobial activity of Plectranthus amboinicus solvent extracts against human pathogenic bacteria and fungi. J Drug Deliv Ther 2019; 9 (03) 36-39
    CrossrefGoogle Scholar
  • 17 Jamshidi N, Cohen MM. The clinical efficacy and safety of tulsi in humans: a systematic review of the literature. Evid Based Complement Alternat Med 2017; 2017: 9217567 DOI: 10.1155/2017/9217567.
    CrossrefPubMedGoogle Scholar
  • 18 Kumar P, , Sangam, Kumar N. Plectranthus amboinicus: a review on its pharmacological and pharmacognostical studies. Am J Physiology Biochem Pharmacol 2020; 10 (02) 56-62
    CrossrefGoogle Scholar
  • 19 Kaliappan ND, Viswanathan PK. et al. Pharmacognostical studies on the leaves of Plectranthus amboinicus (lour) spreng. Int J Green Pharmacy 2008; 2 (03) 182-184
    CrossrefGoogle Scholar
  • 20 James JP, Jyothi D, Priya S. In silico screening of phytoconstituents with antiviral activities against SARS-COV-2 main protease, Nsp12 polymerase, and Nsp13 helicase proteins. Lett Drug Design & Discovery 2021; 18 (08) 841-857
    CrossrefGoogle Scholar
  • 21 Molinspiration Cheminformatics free web services, Slovensky Grob, Slovakia. [Online]. Accessed May 27, 2023 at: https://www.molinspiration.com
    Google Scholar
  • 22 Lipinski CA. Lead- and drug-like compounds: the rule-of-five revolution. Drug Discov Today Technol 2004; 1 (04) 337-341
    CrossrefPubMedGoogle Scholar
  • 23 Jorgensen WL. The many roles of computation in drug discovery. Science 2004; 303 (5665): 1813-1818
    CrossrefPubMedGoogle Scholar
  • 24 Ioakimidis L, Thoukydidis L, Mirza A, Naeem S, Reynisson J. Benchmarking the reliability of QikProp. Correlation between experimental and predicted values. QSAR Comb Sci 2008; 27 (04) 445-456
    CrossrefGoogle Scholar
  • 25 Mawere C. G Kumar S. In silico design and analysis of G. Moniliformis class II hydrophobin inhibitor as a potential antifungal drug. Mater Today Proc 2015; 2: 4429-4435
    CrossrefGoogle Scholar
  • 26 Banerjee P, Eckert AO, Schrey AK, Preissner R. ProTox-II: a webserver for the prediction of toxicity of chemicals. Nucleic Acids Res 2018; 46 (W1): W257-W263 DOI: 10.1093/nar/gky318.
    CrossrefPubMedGoogle Scholar
  • 27 Husain A, Ahmad A, Khan SA, Asif M, Bhutani R, Al-Abbasi FA. Synthesis, molecular properties, toxicity and biological evaluation of some new substituted imidazolidine derivatives in search of potent anti-inflammatory agents. Saudi Pharm J 2016; 24 (01) 104-114
    CrossrefPubMedGoogle Scholar
  • 28 James JP, Monteiro SR, Sukesh KB, Varun A. Design and Identification of Lead Compounds Targeting Nipah G Attachment Glycoprotein by In Silico Approaches. J Pharm Res Int 2021; 33 (40A): 156-169
    CrossrefGoogle Scholar
  • 29 Hodgson J. ADMET–turning chemicals into drugs. Nat Biotechnol 2001; 19 (08) 722-726
    CrossrefPubMedGoogle Scholar
  • 30 Kumar A, Singh S, Jain S, Kumar P. Synthesis, antimicrobial evaluation, QSAR and in Silico ADMET studies of decanoic acid derivatives. Acta Pol Pharm 2011; 68 (02) 191-204
    PubMedGoogle Scholar
  • 31 Qiu X, Janson CA, Smith WW. 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
    CrossrefPubMedGoogle Scholar
  • 32 James JP, Aiswarya TC, Shenoy SP. et al. Synthesis and in silico study of new azetidinones against non-small cell lung cancer by EGFR inhibition. TJPS 2022; 46 (05) 595-606
    Google Scholar