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
Abstract
Quercetin (3,3′,4′,5,7-Pentahydroxyflavone) is the one among the bioactive secondary metabolite (BASM) in neem seed of Azadirachta indica A. Juss. Quercetin (Que) and its derivatives hold promising pharmacological effects. Antidiabetic, anti-inflammatory, antioxidant, antimicrobial, anti-Alzheimer’s, antiarthritic, cardiovascular, and wound-healing effects of Que have been extensively investigated, recently lot of work has been carried out on its anticancer activity against different cancer cell lines. Recently, in silico/ in vitro studies have demonstrated that Que interferes with different stages of coronavirus entry and replication cycle (PLpro, 3CLpro, and NTPase/helicase). Due to its pleiotropic effects in human health and disease and lack of systemic toxicity, Que and its derivatives could be tested for their efficacy on human target system in future clinical trials. In the present study, an attempt has been made to evaluate the physicochemical, druggable properties of Que from A. indica to prospect its ADMET properties.
Keywords: NEEM; Azadirachta indica; Quercetin; Pharmacoinformatics; ADMET; Drug-Likeness; Toxicology
Keywords:
NEEM, Azadirachta indica, Quercetin, Pharmacoinformatics, ADMET, Drug-Likeness, ToxicologyDOI
https://doi.org/10.22270/jddt.v11i5-S.5026References
Kalaivani T, Meignanam E, Premkumar N, Siva R, Vijayakumar V, Rajasekaran C, Ramya S, Jayakumararaj R. Studies on hepatoprotective properties of leaf extracts of Azadirachta indica A. Juss (Meliaceae). Ethnobotanical Leaflets 2009; 2009(1):20.
Schmutterer H, Ascher KR. Neem tree (Azadirachta indica A. Juss.) and other meliaceous plants VCH; 199 https://doi.org/10.1002/3527603980
Loganathan T, Barathinivas A, Soorya C, Balamurugan S, Nagajothi TG, Jayakumararaj R. GCMS Profile of Bioactive Secondary Metabolites with Therapeutic Potential in the Ethanolic Leaf Extracts of Azadirachta indica¬: A Sacred Traditional Medicinal Plant of INDIA. Journal of Drug Delivery and Therapeutics. 2021; 11(4-S):119-26. https://doi.org/10.22270/jddt.v11i4-S.4967
Zeenat F, Ravish MS, Ahmad W, Ahmad I. Therapeutic, phytochemistry and pharmacology of Azadirachta indica: A review. Int J Unani Integr Med. 2018; 2(1):20-8.
Biswas K, Chattopadhyay I, Banerjee RK, Bandyopadhyay U. Biological activities and medicinal properties of neem (Azadirachta indica). Current Science. 2002:1336-45.
Negi PS, Jayaprakasha GK, Jena BS. Distribution and introduction cultivation state of Azadirachta indica Food Chemistry. 2002; 80:293-7.
Yan_ping ZH, Yong_qi LA, Xing_ming PE, Juan LI. Global Distribution and Introduction Cultivation State of Azadirachta indica [J]. Forest Inventory and Planning. 2002; 3(2)5-9.
Ramya S, & Jayakumararaj R. Antifeedant activity of selected ethno-botanicals used by tribals of Vattal Hills on Helicoverpa armigera (Hübner). Journal of Pharmacy Research. 2009; 2(8):1414-1418.
Islas JF, Acosta E, Zuca G, Delgado-Gallegos JL, Moreno-Treviño MG, Escalante B, Moreno-Cuevas JE. An overview of Neem Azadirachta indica and its potential impact on health. Journal of Functional Foods. 2020; 74:104171. https://doi.org/10.1016/j.jff.2020.104171
Rahmani A, Almatroudi A, Alrumaihi F, Khan A. Pharmacological and therapeutic potential of neem (Azadirachta indica). Pharmacognosy Reviews. 2018; 12(24). https://doi.org/10.4103/phrev.phrev_8_18
Bhowmik D, Chiranjib YJ, Tripathi KK, Kumar KS. Herbal remedies of Azadirachta indica and its medicinal application. J Chem Pharm Res. 2010; 2(1):62-72.
Chen J, Fan X, Zhu J, Song L, Li Z, Lin F, Yu R, Xu H, Zi J. Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic activity. Acta pharmaceutica sinica B. 2018; 8(4):639-44. https://doi.org/10.1016/j.apsb.2017.12.009
Khanal P, Magadum P, Patil BM, Hullatti KK. In silico docking study of Limonoids from Azadirachta indica with pfpk5: A Novel Target for Plasmodium falciparum. Indian Journal of Pharmaceutical Sciences. 2019; 81(2):326-32. https://doi.org/10.36468/pharmaceutical-sciences.514
Kraus W, Cramer R, Sawitzki G. Tetranortriterpenoids from the seeds of Azadirachta indica Phytochemistry. 1981; 20(1):117-20. https://doi.org/10.1016/0031-9422(81)85229-6
Willy S, Nilan R, Kekare MB, Vikas V. Estimation of two bioactive compounds from Azadirachta indica A. Juss. leaves using HPLC. International Journal of Pharma and Bio Sciences. 2010; 1(2).
Mitra CR, Garg HS, Pandey GN. Identification of nimbidic acid and nimbidinin from Azadirachta indica Phytochemistry. 1971; 10(4):857-64. https://doi.org/10.1016/S0031-9422(00)97156-5
Moga MA, Bălan A, Anastasiu CV, Dimienescu OG, Neculoiu CD, Gavriș C. An overview on the anticancer activity of Azadirachta indica (Neem) in gynecological cancers. International journal of molecular sciences. 2018; 19(12):3898. https://doi.org/10.3390/ijms19123898
Baildya N, Khan AA, Ghosh NN, Dutta T, Chattopadhyay AP. Screening of potential drug from Azadirachta indica (Neem) extracts for SARS-CoV-2: an insight from molecular docking and MD-simulation studies. Journal of Molecular Structure 2021; 1227:129390 https://doi.org/10.1016/j.molstruc.2020.129390
Eid A, Jaradat N, Elmarzugi N. A Review of chemical constituents and traditional usage of Neem plant (Azadirachta indica). Palestinian Medical and Pharmaceutical Journal. 2017; 2(2):75-81.
Hossain MA, Al-Toubi WA, Weli AM, Al-Riyami QA, Al-Sabahi JN. Identification and characterization of chemical compounds in different crude extracts from leaves of Omani neem. Journal of Taibah University for Science. 2013; 7(4):181-8. https://doi.org/10.1016/j.jtusci.2013.05.003
Kumar R, Sharma S, Devi L. Investigation of total phenolic, flavonoid contents and antioxidant activity from extracts of Azadirachta indica of Bundelkhand Region. Int. J. Life. Sci. Scienti. Res. eISSN. 2018; 2455(1716):1716. https://doi.org/10.21276/ijlssr.2018.4.4.10
Siddiqui BS, Afshan F, Faizi S, Naqvi SN, Tariq RM. Two insecticidal tetranortriterpenoids from Azadirachta indica Phytochemistry. 2000; 53(3):371-6. https://doi.org/10.1016/S0031-9422(99)00548-8
Awolu OO, Obafaye RO, Ayodele BS. Optimization of solvent extraction of oil from neem Azadirachta indica and its characterizations. Journal of Scientific Research and Reports. 2013; 10:304-314 https://doi.org/10.9734/JSRR/2013/3705
Agrawal S, Popli DB, Sircar K, Chowdhry A. A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer. Journal of Oral Biology and Craniofacial Research. 2020 Apr 1; 10(2):206-9. https://doi.org/10.1016/j.jobcr.2020.04.007
Agrawal S, Popli DB, Sircar K, Chowdhry A. A review of the anticancer activity of Azadirachta indica (Neem) in oral cancer. Journal of Oral Biology and Craniofacial Research. 2020 Apr 1; 10(2):206-9. https://doi.org/10.1016/j.jobcr.2020.04.007
Upadhyay SN, Dhawan S, Garg S, Talwar GP. Immunomodulatory effects of neem Azadirachta indica oil. International Journal of Immunopharmacology. 1992; 14(7):1187-93. https://doi.org/10.1016/0192-0561(92)90054-O
Muhammad A, Kashere MA. NEEM, Azadirachta indica L.(A. Juss): an eco-friendly botanical insecticide for managing farmers 'insects pest problems - a review. FUDMA Journal of Sciences. 2020; 4(4):484-91. https://doi.org/10.33003/fjs-2020-0404-506
Benelli G, Canale A, Toniolo C, Higuchi A, Murugan K, Pavela R, Nicoletti M. Neem (Azadirachta indica): towards the ideal insecticide?. Natural product research. 2017; 31(4):369-86. https://doi.org/10.1080/14786419.2016.1214834
Schmutterer H. Properties and potential of natural pesticides from the neem tree, Azadirachta indica Annual review of entomology. 1990; 35(1):271-97. https://doi.org/10.1146/annurev.en.35.010190.001415
Gupta SC, Prasad S, Tyagi AK, Kunnumakkara AB, Aggarwal BB. Neem (Azadirachta indica): An Indian traditional panacea with modern molecular basis. Phytomedicine. 2017; 34:14-20. https://doi.org/10.1016/j.phymed.2017.07.001
Hashmat I, Azad H, Ahmed A. Neem (Azadirachta indica A. Juss) - A nature's drugstore: an overview. Int Res J Biol Sci. 2012; 1(6):76-9.
Ramya S, Neethirajan K & Jayakumararaj R. Profile of bioactive compounds in Syzygium cumini-a review. J. Pharm. Res 2012; 5(8):4548-4553.
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
Saleem S, Muhammad G, Hussain MA, Bukhari SN. A comprehensive review of phytochemical profile, bioactives for pharmaceuticals, and pharmacological attributes of Azadirachta indica Phytotherapy research. 2018; 32(7):1241-72. https://doi.org/10.1002/ptr.6076
Sarkar S, Singh RP, Bhattacharya G. Exploring the role of Azadirachta indica (neem) and its active compounds in the regulation of biological pathways: an update on molecular approach. 3 Biotech. 2021; 11(4):1-2. https://doi.org/10.1007/s13205-021-02745-4
Ahmad S, Maqbool A, Srivastava A, Gogol S. Biological detail and therapeutic effect of Azadirachta indica (neem tree) products-a review. J. Evidence Based Med. Healthcare. 2019; 6(22):1607-1612. https://doi.org/10.18410/jebmh/2019/324
Alzohairy MA. Therapeutics role of Azadirachta indica (Neem) and their active constituents in diseases prevention and treatment Evidence-Based Complementary and Alternative Medicine. 2016; 2016 https://doi.org/10.1155/2016/7382506
Venugopal V. Antidermatophytic activity of neem Azadirachta indica leaves in vitro. Indian Journal of Pharmacology. 1994; 26(2):141.
Tembe-Fokunang EA, Charles F, Kaba N, Donatien G, Michael A, Bonaventure N. The potential pharmacological and medicinal properties of neem (Azadirachta indica A. Juss) in the drug development of phytomedicine Journal of Complementary and Alternative Medical Research. 2019; 23:1-8 https://doi.org/10.9734/jocamr/2019/v7i130093
Srivastava SK, Agrawal B, Kumar A, Pandey A. Phytochemicals of Azadirachta indica source of active medicinal constituent used for cure of various diseases: A Review. Journal of Scientific Research. 2020; 64(1):385-90. https://doi.org/10.37398/JSR.2020.640153
Krist S. Neem Oil. InVegetable Fats and Oils 2020 (pp. 467-473). Springer, Cham. https://doi.org/10.1007/978-3-030-30314-3_75
Jain S, Ganeshpurkar A, Dubey N. Molecular Docking of some Neem Constituents with COX-2 and NOs: An in silico Study. Pharmacognosy Communications. 2020 Jul 1; 10(3):134-5. https://doi.org/10.5530/pc.2020.3.26
Rajasekaran C, Meignanam E, Vijayakumar V, Kalaivani T, Ramya S, Premkumar N, Siva R, Jayakumararaj R Investigations on antibacterial activity of leaf extracts of Azadirachta indica A. Juss (Meliaceae): a traditional medicinal plant of India. Ethnobotanical Leaflets. 2008; 2008(1):161-.167
Roy S, Bhattacharyya P. Possible role of traditional medicinal plant Neem Azadirachta indica for the management of COVID-19 infection. Int. J. Res. Pharm. Sci.. 2020:122-5. https://doi.org/10.26452/ijrps.v11iSPL1.2256
Patel SM, Venkata KC, Bhattacharyya P, Sethi G, Bishayee A. Potential of neem (Azadirachta indica L.) for prevention and treatment of oncologic diseases. In Seminars in cancer biology 2016; 40,100-115. Academic Press. https://doi.org/10.1016/j.semcancer.2016.03.002
Paul R, Prasad M, Sah NK. Anticancer biology of Azadirachta indica L (neem): a mini review. Cancer biology & therapy. 2011; 12(6):467-76. https://doi.org/10.4161/cbt.12.6.16850
Lloyd AC, Menon T, Umamaheshwari K. Anticandidal activity of Azadirachta indica Indian Journal of Pharmacology. 2005; 37(6):386. https://doi.org/10.4103/0253-7613.19076
Waheed A., Miana G.A., Ahmad S.I. Clinical investigation of hypoglycemic effect of seeds of Azadirachta indica in type 2 (NIDDM) diabetes mellitus. Pak. J. Pharm. Sci. 2006; 19:322-325.
Khan MR, Chonhenchob V, Huang C, Suwanamornlert P. Antifungal Activity of Propyl Disulfide from Neem (Azadirachta indica) in Vapor and Agar Diffusion Assays against Anthracnose Pathogens (Colletotrichum gloeosporioides and Colletotrichum acutatum) in Mango Fruit. Microorganisms. 2021 Apr; 9(4):839. https://doi.org/10.3390/microorganisms9040839
Afolabi OJ, Simon-Oke IA, Oladokun OI. Antiplasmodial Activity of Ethanolic Extract of Neem Leaf (Azadirachta indica) in Albino Mice Infected with Plasmodium berghei. Int Arch Clin Pharmacol. 2021; 7:024. https://doi.org/10.23937/2572-3987.1510024
Dharshini AD, Muralidharan NP. Neem as antiviral agents. International Journal of Pharmaceutical Research. 2020 Jan 1; 12. https://doi.org/10.31838/ijpr/2020.SP1.017
Patil SM, Shirahatti PS, Ramu R, Prasad N. Azadirachta indica A. Juss (neem) as a contraceptive: An evidence-based review on its pharmacological efficiency. Phytomedicine. 2021; 19:153596. https://doi.org/10.1016/j.phymed.2021.153596
Ramya S, Jepachanderamohan PJ, Kalayanasundaram M, Jayakumararaj R. In vitro antibacterial prospective of crude leaf extracts of Melia azedarach Linn. against selected bacterial strains. Ethnobotanical Leaflets. 2009; 2009(1):32.
Isdadiyanto S, Sitasiwi AJ, Mardiati SM. The lipid profile of rats (Rattus norvegicus L.) induced by high fat ration after exposed to ethanolic neem (Azadirazchta indica) leaf extract. Journal of Physics: Conference Series 2020; 1524(1):012126). IOP Publishing. https://doi.org/10.1088/1742-6596/1524/1/012126
Dwivedi VD, Bharadwaj S, Afroz S, Khan N, Ansari MA, Yadava U, Tripathi RC, Tripathi IP, Mishra SK, Kang SG. Anti-dengue infectivity evaluation of bioflavonoid from Azadirachta indica by dengue virus serine protease inhibition. Journal of Biomolecular Structure and Dynamics. 2021; 39(4):1417-30. https://doi.org/10.1080/07391102.2020.1734485
Kaushik N, Singh BG, Tomar UK, Naik SN, Vir S, Bisla SS, Sharma KK, Banerjee SK, Thakkar P. Regional and habitat variability in azadirachtin content of Indian neem (Azadirachta indica A. Juss). Current Science. 2007:1400-1406.
Tomar UK, Singh G, Kaushik N. Screening Azadirachta indica tree for enhancing azadirachtin and oil contents in dry areas of Gujarat, India. Journal of Forestry Research. 2011; 22(2):217-24. https://doi.org/10.1007/s11676-011-0153-0
Zheng Y, Wu J, Wang Y, Peng X, Zhang Y. Seed yield and azadirachtin content of Azadirachta indica in four ecosystems of southwest China. Industrial Crops and Products. 2018; 122:23-27. https://doi.org/10.1016/j.indcrop.2018.05.040
Gahukar RT. Factors affecting content and bioefficacy of neem (Azadirachta indica A. Juss.) phytochemicals used in agricultural pest control: a review. Crop Protection. 2014; 62:93-99. https://doi.org/10.1016/j.cropro.2014.04.014
Salehi B, Machin L, Monzote L, Sharifi-Rad J, Ezzat SM, Salem MA, Merghany RM, El Mahdy NM, Kılıç CS, Sytar O, Sharifi-Rad M. Therapeutic potential of quercetin: New insights and perspectives for human health. Acs Omega. 2020; 5(20):11849-72. https://doi.org/10.1021/acsomega.0c01818
Elmi A, Mohamed AS, Siddiqui N, AL Jawad S, Nour M, Miganeh I, Javed S. Identification of potential inhibitors of SARS-CoV-2 from Artemisia annua compounds by In silico evaluation and their density functional theory (DFT). JDDT 2021; 11(1-s):71-2. https://doi.org/10.22270/jddt.v11i1-s.4702
Borkotoky S, Banerjee M. A computational prediction of SARS-CoV-2 structural protein inhibitors from Azadirachta indica (Neem). Journal of Biomolecular Structure and Dynamics. 2020; 8:1-1. https://doi.org/10.1080/07391102.2020.1774419
Muhammed D, Odey BO, Alozieuwa BU, Alawode RA, Okunlola BM, Ibrahim J, Lawal A, Berinyuy EB. Azadirachtin-A a bioactive compound from Azadirachta indica is a potential inhibitor of SARS-CoV-2 main protease. AROC in Pharmaceutical and Biotechnology. 2021; 1(1):1-8. https://doi.org/10.53858/arocpb01010108
Fernandes SR, Barreiros L, Oliveira RF, Cruz A, Prudêncio C, Oliveira AI, Pinho C, Santos N, Morgado J. Chemistry, bioactivities, extraction and analysis of azadirachtin: State-of-the-art. Fitoterapia. 2019; 134:141-50. https://doi.org/10.1016/j.fitote.2019.02.006
Adegbola PI, Semire B, Fadahunsi OS, Adegoke AE Molecular docking and ADMET studies of Allium cepa, Azadirachta indica and Xylopia aethiopica isolates as potential anti-viral drugs for Covid-19. Virus Disease. 2021; 32(1):85-97. https://doi.org/10.1007/s13337-021-00682-7
Durán-Iturbide NA, Díaz-Eufracio BI, Medina-Franco JL. In silico ADME/Tox profiling of natural products: A focus on BIOFACQUIM. ACS omega. 2020; 5(26):16076-84. https://doi.org/10.1021/acsomega.0c01581
Medina-Franco JL, Saldívar-González FI. Cheminformatics to characterize pharmacologically active natural products. Biomolecules. 2020; 10(11):1566. https://doi.org/10.3390/biom10111566
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):66-3. https://doi.org/10.22270/jddt.v11i4.4890
Gleeson M P. Generation of a set of simple, interpretable ADMET rules of thumb J Med Chem, 2008, 51(4):817-34. https://doi.org/10.1021/jm701122q
Xiong G, Wu Z, Yi J, Fu L, Yang Z, Hsieh C, Yin M, Zeng X, Wu C, Lu A, Chen X. ADMETlab 2.0: an integrated online platform for accurate and comprehensive predictions of ADMET properties. Nucleic Acids Research. 2021; Apr 24. https://doi.org/10.1093/nar/gkab255
Govindachari TR. Chemical and biological investigations on Azadirachta indica (the neem tree). Current science. 1992; 63(3):117-22.
Lakshmi T, Krishnan V, Rajendran R, Madhusudhanan N. Azadirachta indica: A herbal panacea in dentistry-An update. Pharmacognosy reviews. 2015; 9(17):41. https://doi.org/10.4103/0973-7847.156337
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
Kadhirvel K, Rajivgandhi P, Narayanan G, Govindaraji V, Kannan K, Vanithaselvi R, Ramya S, Jayakumararaj R. Investigations on Anti-diabetic medicinal plants used by tribal inhabitants of Nalamankadai, Chitteri Reserve Forest, Dharmapuri, India. Ethnobotanical Leaflets. 2010; 2010(3):2.
Published
Abstract Display: 1008 
PDF Downloads: 874 PDF Downloads: 336 How to Cite
Issue
Section
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).
How to Cite
.