MOLECULAR DOCKING & IN SILICO ADME STUDIES OF PHYTOCHEMICAL CONSTITUENTS ADHATHODA VASICA AGAINST SUPERFAMILY SUBGROUP OF TREHALOSE -6- PHOSPHATE PHOSPHATASE.
-
Afroz Patan
Department of Pharmacy practice, Ratnam Institute of Pharmacy , Pidathapolur (V&P), Muthukur (M) , SPSR Nellore District -524 346.
afrozpathanpharma@gmail.com
Abstract
Trehalose-6-phosphate phosphatase (TPP) enzymes are used by many pathogenic microorganisms in their process of infection and proliferation to biosynthesise the sugar trehalose from trehalose-6-phosphate (T6P). As a result, the current work uses in silico techniques to build novel candidate medications that block TPP. Adhathoda Vasica commonly known as Vasaka or Malabar nut. It belongs to the Acanthaceae family and has been used in traditional Ayurvedic and Unani medicine for centuries are a promising source of phytochemicals, particularly vasicine and vasicinone, quinazoline alkaloids, including vasicinolone, vasicol, and adhatodine. These compounds are known for their bronchodilatory and expectorant properties. Swiss ADME software was accessed in a web server that displays the Submission page of Swiss ADME in Google was used to estimate individual ADME behaviors of the compounds from the plant. Advanced ADME studies were performed for confirmation of vasicine, adhatodine and Epitaraxenol compounds to be orally bioavailable or not. The present work is an approach to design new generation candidate drugs to inhibit TPP through in silico methods on pulmonary activity using 1YMQ. Docking studies of 3D model of TPP with many phytochemicals revealed most of them have good binding affinity to an enzyme with adothodine exhibiting highest affinity with Docking score -7.4 having more responsible for inhibiting infection on pulmonary activity compared to the compound Vasicine with the docking score: -6.5, and epitaraxerol with the docking score: -7.0. Hence the current research proves that the phytochemical compound of Adhatoda vasica act as promising lead as Trehalose-6-phosphate phosphatase
References
2. Arabind KVK, Garg RK, Singh L, Chauhan SS. Pharmacognostic Study and Establishment of Quality Parameters of Leaves of Adhatoda vasica. Linn. Journal of Medicinal Plants Studies 2013; 1(3):35-40.
3. Jain MP, VNG, Atal CK, Recent advances in vasaka alkaloids- a review Indian drugs 1984; 21:313
4. Santosh Kumar Singh, Jay Ram Patel, Pharmacognostic study and phytochemical screening of leaf of Adhatoda vasica (Acanthaceae), Journal of Medicinal Plants Studies 2014; 2(4): 29-31
5. Atal, C.K. 1980. Chemistry and Pharmacology of Vasicine - A new oxytocic and abortifacient, Indian Drugs, 15(2), 15-18.
6. Sayeed, A., Madhukar, G., Maksood, A., Mhaveer, S., Md. Tanwir, A. and Shahid, H.A. 2009. A Phyto- pharmacological overview on Adhatoda zeylanica Medic. Syn. A. vasica (Linn.) Nees. Natural Product Radiance, 8(5): 549-554.
7. Patel, V.K. and Venkata-Krishna- Bhatt, H. 1984. In vitro study of anti- microbial activity of Adhatoda vasica (L) (Leaf extract) on gingival inflammation- A preliminary report. Ind. J. Med. Sci., 38: 70-72.
8. Vinothapooshan, G. and Sundar, K. 2010. Hepatoprotective activity of Adhatoda vasica leaves against carbontetrachloride induced toxicity. Pharmacologyonline, 2: 551-558.
9. Chakrabarty, A. and Brantner, A.H. 2001. Study of alkaloids from Adhatoda vasica Nees on their anti-inflammatory activity. Phytother. Res., 15: 532-534.
10. Rahman, S.M.M., Sen, P.K., Afroz, F. and Sultana, K. 2004. In vitro propagation of Adhatoda vasica from shoot tip. Mol. Biol. Biotechnol. j., 2(1&2): 33-35.
11. Gupta, O.P., Sharma, M.L., Ghattak, B.J.R. and Atal, C.K. 1977. Pharmacological investigation of vasicine and vasinone- The alkaloids of Adhatoda vasica. Indian J. Med. Res., 66: 680–691.
12. Ajay Sharma, Overview of Phytochemistry and Pharmacology of Adhatoda vasica, International Journal of Advanced in Management, Technology and Engineering Sciences Volume 8, Issue III, March/2018, ISSN NO: 2249-7455
13. H. R. Umesh, Molecular docking studies of phytochemicals against trehalose–6– phosphate phosphatases of pathogenic microbes, Beni-Suef University Journal of Basic and Applied Sciences (2020) 9:5
14. Kormish JD, McGhee JD (2005) The C. elegans lethal gut-obstructed gob-1 gene is trehalose-6-phosphate phosphatase. Dev Biol. 287(1):35–47
15. Susheela K, Prashant KS, Mohd S, Manisha P, Shailja MB (2012) In vitro silencing of Brugia malayi trehalose-6-phosphate phosphatase impairs embryogenesis and in vivo development of infective larvae in jirds. PLoS Negl Trop Dis. 6(8):e1770
16. Cross M, Lepage R, Rajan S, Biberacher S, Young ND, Kim BN, Coster MJ, Gasser RB, Kim JS, Hofmann A (2017) Probing function and structure of trehalose-6-phosphate phosphatases from pathogenic organisms suggests distinct molecular groupings. FASEB J. 31(3):920–926
17. Umesh HR, Ramesh KV (2016) Purification, characterization and partial structure determination of native trehalose-6-phosphate phosphatase from maize genotype EC 558706 under salt stress condition. Int j pharma and BioSci 7(3):(B)1263–1273
18. Oleg T, Arthur JO (2010) Auto Dock 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
19. Kancharla Bhanukiran , Ravi Singh , Vasicinone, a pyrroloquinazoline alkaloid from Adhatoda vasica Nees enhances memory and cognition by inhibiting cholinesterases in Alzheimer’s disease Phytomedicine Plus 3 (2023) 100439
20. Lu, Q., Gu, W., Luo, C., Wang, L., Hua, W., Sun, Y., Tang, L., Phytochemical characterization and hepatoprotective effect of active fragment from Adhatoda vasica Nees. against tertbutyl hydroperoxide induced oxidative impairment via activating AMPK/p62/Nrf2 pathway, Journal of Ethnopharmacology, https://doi.org/10.1016/j.jep.2020.113454.
21. A. Daina, O. Michielin and V. Zoete, SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules, Sci. Rep., 2017, 7, 42717, DOI: 10.1038/srep42717
22. J. Eberhardt, D. Santos-Martins, A. F. Tillack and S. Forli, AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings, J. Chem. Inf. Model., 2021, 61(8), 3891–3898, DOI: 10.1021/acs.jcim.1c00203
23. S.K. Ali, A.R. Hamed, Kinetics and molecular docking of vasicine from Adhatoda vasica: An acetylcholinesterase inhibitor for Alzheimer's disease, South African Journal of Botany 104 (2016) 118–124
24. S.S. Swain, M.C. Sahu, R.N. Padhy, In silico attempt for adduct agent(s) against malaria: combination of chloroquine with alkaloids of Adhatoda vasica, Computer Methods and Programs in Biomedicine (2015), http://dx.doi.org/10.1016/j.cmpb.2015.06.005
25. Ubonwan Pongprayoon Claeson, Adhatoda vasica: a critical review of ethnopharmacological and toxicological data, Journal of Ethnopharmacology 72 (2000) 1–20.
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All the articles are published in AJMNS are under Creative Commons License. Any further distribution or use of content published under CC BY-NC 4.0 must maintain attribution to the author(s) and the published article’s title, journal citation Creative Commons Attribution-NonCommercial 4.0 Unported License.
