ANTIOXIDANT, ANTIMICROBIAL, ANTIPROLIFERATIVE ACTIVITIES AND IN SILICO DRUG LIKENESS PREDICTION OF PURIFIED MHH COMPOUND, ISOLATED FROM MILLINGTONIA HORTENSIS LINN
Objective: To investigate the antioxidant, antimicrobial, antiproliferative activities and in silico drug likeness prediction of the MHH compound.
Methods: The antioxidant, antimicrobial and antiproliferative activities of the MHH compound have been evaluated by 1,1-Diphenyl-2-picryl hydrazyl (DPPH) and Ferric Reducing Antioxidant Power (FRAP) assays, agar well diffusion assay and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay respectively. The cytotoxicity activity and in silico drug likeness prediction of the MHH compound have been studied.
Results: The DPPH radical scavenging activity and the total antioxidant power of the MHH compound were found to be 92.48%Â±2.06 and 10.698Â±0.23 mM Fe (II)/g respectively. The antimicrobial activity of MHH compound against Escherichia coli, Klebsiella pneumonia, Proteus vulgaris, Salmonella typhi, Staphylococcus aureus and Streptomyces griseus, Candida albicans, Aspargillus flavus and the zones of inhibition were found to be 16.83 mm, 19.83 mm, 15.23 mm, 16.79 mm, 13.57 mm, 19.65 mm, 18.66 mm and 14.79 mm respectively. The IC50 values of the MHH compound for HeLa and HCT-15 cell lines were found to be 371.92 Î¼g/ml and 112.06 Î¼g/ml respectively. The LC50 value of MHH compound was 218.765Âµg/ml and 152.78Âµg/ml which is considered as moderately cytotoxic and toxic respectively when incubated at 24 h and 48 h. The drug likeness and bioactivity scores of the MHH compound were found to be within the range and followed Lipinskiâ€™s rule.
Conclusion: This study concludes that the MHH compound has significant biological activities and can be used as the therapeutic agent.
2. Kelly EH, Anthony RT, Dennis JB. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem 2002;13:572â€“84.
3. Kumar S, Mishra A, Pandey AK. Antioxidant mediated protective effect of Parthenium hysterophorus against oxidative damage using in vitro models. BMC Complementary Altern Med 2013;13:120.
4. Pandey AK. Anti-staphylococcal activity of a pan-tropical aggressive and obnoxious weed Pariheniumhisterophorus: an in vitro study. Natl Acad Sci 2007;30:383â€“6.
5. Cook NC, Samman S. Review: flavonoids-chemistry, metabolism, cardio protective effects and dietary sources. J Nutr Biochem 1996;7:66â€“76.
6. Rice-Evans CA, Miller NJ, Bolwell PG, Broamley PM, Pridham JB. The relative antioxidant activities of plant derived polyphenolic flavonoids. Free Radical Res 1995;22:375â€“83.
7. Kumar S, Gupta A, Pandey AK. Calotropis procera root extract has capability to combat free radical mediated damage. ISRN Pharmacol 2013;1-8. doi.org/10.1155/2013/691372. [Article in Press]
8. Kumar S, Pandey AK. Phenolic content, reducing power and membrane protective activities of Solanum xanthocarpum root extracts. Vegetos 2013;26:301â€“7.
9. Tahia H Saleem, Hamdy N Eltalawy, Ahmed E Ahmed, Nagla H Abu-faddan, Nahed A Mohamed, Ayat A Sayed, et al. Glycogen storage disease type-I among pediatric patients in Upper Egypt. Gl Adv Res J Med Sci 2014;3:281-90.
10. Haraguchi H, Tanimoto K, Tamura Y, Mizutani K, Kinoshita T. Mode of antibacterial action of retrochalcones from Glycyrrhiza inata. Phytochem 1998;48:125â€“9.
11. Tomas-Berberan F, Iniesta-Sanmartin E, Tomas-Lorente F, Rumbero A. Antimicrobial Phenolic compounds from three Spanish Helichrysum species. Phytochem 1990;29:1093-5.
12. Iinuma M, Okawa Y, Tanaka T. Three new cinnamylphenols in heartwood of Erythrina crista-galli. Phytochem 1994;37:1153-5.
13. Dahl-Jensen D, Mosegaard K, Gundestrup N, Clow GD, Johnsen SJ, Hansen AW, et al. Past temperatures directly from the Greenland ice sheet. Science 1998;282:268-71.
14. Kaneda N, Pezzuto JM, Soejarto DD, Kinghorn AD, Farnwort NR, Santisuk T, et al. Plant anticancer agents, XLVII. New cytotoxic flavanoids from Muntingia calabura roots. J Nat Prod 1991;54:196-206.
15. Lee IK, Kim CJ, Song KS, Kim HM, Koshino H, Uramoto M, et al. Cytotoxic benzyl dihydroflavonols from Cudrania tricuspidata. Phytochem 1996;41:213-6.
16. Silva GL, Chai H, Gupta MP, Farnsworth NR, Cordell GA, Pezzuto JM, et al. Cytotoxic biflavonoids from Selaginella willdenowii. Phytochem 1995;40:129-34.
17. Zheng GQ. Cytotoxic terpenoids and flavonoids from Artemisia annua. Planta Med 1994;60:54-7.
18. Kandaswarmi C, Perkins E, Drzewiecki G, Soloniuk DS, Middleton, E Jr. Differential inhibition of proliferation of human squamous cell carcinoma, gliosarcoma and embryonic fibroblast-like lung cells in culture by plant flavonoids. Anti-Cancer Drugs 1992;3:525-30.
19. Mahesh Kumar MVS, Prasad Talluri VSSL, Rajagopal SV. Purification and characterization of bioactive compound from the methanolic leaf extract of Millingtonia hortensis Linn. Int J Pharm Biol Sci 2015;6:248-58.
20. Siva Kumar K, Raja Gopal SV. Radical scavenging activity of green algal species. J Pharm Res 2008;4:723-5.
21. Rajagopal SV, Rao AP, Raman BV, Rao MR, Sankar AU, Kumari AS, et al. Biochemical and antibacterial studies on green algae of Visakhapatnam coast. J Appl Microbiol 2008;2:573-8.
22. Raja Gopal SV, Raman BV, Bhaskar Reddy I, Siva Kumar K. Antioxidants and free radical scavenging activity of brown algae of visakhapatnam coast. Asian J Chem 2008;20:5293-300.
23. Cuendet M, Hostettmann K, Potterat O. Iridoid glucosides with free radical scavenging properties from Fragrea blumei. Helv Chim Acta 1997;80:1144â€“51.
24. Benzie FF, Strain JJ. Ferric reducing antioxidant power assay, Direct measure of total antioxidant activity of biological fluids and modified version for simultaneous measurement of total antioxidant power and ascorbic acid concentration. Methods Enzymol 1999;299:15-23.
25. Olurinola PF. A Laboratory manual of Pharmaceutical Microbiology, Idu, Abuja, Nigeria; 1996. p. 69-105.
26. Murry PR, Baron EJ, Pfaller MA, Tenover FC, Yolken HR. Manual of clinical Microbiology. 6th edition. ASM Press: Washington, DC; 1995. p. 15-8.
27. Perez C, Paul M, Bazerque P. Antibiotic assay by agar-well diffusion method. Acta Biol Med Exp 1990;15:113-5.
28. Mosman T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 1983;65:55â€“63.
29. Meyer BN, Ferrigni NR, Putnam JE, Jacobsen LB, McLaughlin JL. Brine shrimp: a convenient general bioassay for active plant constituents. Planta Med 1982;54:31.
30. Finney DJ. Probit analysis. 3rd Ed. Cambridge: Cambrige University Press; 1971.
31. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 2001;46:3-26.
32. Lipinski CA. Drug discovery today. Technologies 2004;1:337-41.
33. Verma A. Lead finding from Phyllanthus debelis with hepatoprotective potentials. Asian Pac J Trop Biomed 2012;3:1735-7.
34. Ertl P, Rohde B, Selzer P. Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J Med Chem 2000;43:3714-7.
35. Molinspiration cheminformatics [homepage on the internet]. Available from: URL: http://www.molinspiration.com. [Last accessed on 05 May 2015]
36. Lipinski CA, Lombardo F, Dominy BW, Feeney PJ. Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Delivery Rev 1997;23:3-25.