MicroBio Pharmaceuticals and Pharmacology | Online ISSN 2209-2161
RESEARCH ARTICLE   (Open Access)

Complexation of Andrographolide, Mirabegron and Suvorexant and Bioactivity Study of the Complexes

Rajia Sultana and Md. Zakir Sultana*

+ Author Affiliations

Microbial Bioactives 2(1) 076-081 https://doi.org/10.25163/microbbioacts.21010A0410130219

Submitted: 04 July 2018  Revised: 06 February 2019  Published: 13 February 2019 

Abstract

Background: There are many ways to synthesize new drug molecules for more potent therapeutic efficacy with minimum side effects. The drugs may exhibit therapeutic effects independently or may interfere with each other. Method: In this study, new drug molecules were synthesized by drug-drug complexation way according to the calculated w/w ratio. The complexes were prepared by solid-mixing method using pestle and mortar by adding equal amount of drugs to each other, then warmed at 50 °C for 4 hours and left at room temperature for overnight to obtain new drug complexes. The new drug complexes were distinguished by Differential Scanning Calorimetry(DSC) and Fourier-transform infrared spectroscopy (FTIR) with the biological activity. Results: The melting endothermic peaks of andrographolide-suvorexant, andrographolide-mirabegron, and suvorexant-mirabegroncomplexes were found at 221.02 °C, 189.49 °C and 115.78 °C, respectively which were different from the melting endotherms of andrographolide, suvorexant and mirabegron at 230.87 °C, 127.09 °C and 140.40 °C, respectively. The FTIR spectra of the formed complexes showed the similar characteristics of the standard drugs. The cytotoxic effect of the drug complexes on HeLa cell line were higher (10% less survived HeLa cell, i.e. > 90 % cell died) than the precursor drug molecules. Conclusion: Our research findings that three new drug compounds were synthesized by complexation way which could be due to interaction of andrographolide and suvorexant; andrographolide and mirabegron, and suvorexant and mirabegron.

Keywords: Drug, Drug-drug Interaction, Synthesis, Differential Scanning Calorimetry, FTIR, Cytotoxicity, Andrographolide, Suvorexant and Mirabegron.

References

Baxter, C. A., Cleator, E., Brands, K. M. J., Edwards, J. S., Reamer, R. A., Sheen, F. J., … Wallace, D. J. (2011). The First Large-Scale Synthesis of MK-4305: A Dual Orexin Receptor Antagonist for the Treatment of Sleep Disorder. Organic Process Research & Development15(2), 367–375.

https://doi.org/10.1021/op1002853

Cáceres, D. D., Hancke, J. L., Burgos, R. A., & Wikman, G. K. (1997). Prevention of common colds with Andrographis paniculata dried extract. A Pilot double blind trial. Phytomedicine4(2), 101–104.

https://doi.org/10.1016/S0944-7113(97)80051-7

Coleman, P. J., Gotter, A. L., Herring, W. J., Winrow, C. J., & Renger, J. J. (2017). The Discovery of Suvorexant, the First Orexin Receptor Drug for Insomnia. Annual Review of Pharmacology and Toxicology57(1), 509–533.

https://doi.org/10.1146/annurev-pharmtox-010716-104837

Deng, W. L. (1978). Preliminary studies on the pharmacology of the Andrographis product dihydroandrographolide sodium succinate. Newsletter Chinese Herbal Medicine8, 26–28.

Ferdous, U. T., Shishir, M. A., Khan, S. N., & Hoq, M. M. (2018). Bacillus spp.: Attractive Sources of Anti-cancer and Anti-proliferative Biomolecules. Microbial Bioactives1(1), E033–E045.

https://doi.org/10.25163/microbbioacts.11005B0408130818

Goodman, L. S. (1996). Goodman and Gilman’s the pharmacological basis of therapeutics (Vol. 1549). McGraw-Hill New York.

Jacobson, L. H., Callander, G. E., & Hoyer, D. (2014). Suvorexant for the treatment of insomnia. Expert Review of Clinical Pharmacology7(6), 711–730.

https://doi.org/10.1586/17512433.2014.966813

Jarukamjorn, K., & Nemoto, N. (2008). Pharmacological Aspects of Andrographis paniculata on Health and Its Major Diterpenoid Constituent Andrographolide. Journal of Health Science54(4), 370–381.

https://doi.org/10.1248/jhs.54.370

Mishra, S. K., Sangwan, N. S., & Sangwan, R. S. (2007). Phcog Rev.: Plant Review Andrographis paniculata (Kalmegh): A Review. Pharmacognosy Reviews1(2), 283–298.

Mohana, S. J., & Umarani, V. (2016). Isolation and Characterisation of Andrographolide from Andrographis Paniculata. World Journal of Pharmacy and Pharmaceutical Sciences5(9), 1954–1961.

Nanduri, S., Nyavanandi, V. K., Sanjeeva Rao Thunuguntla, S., Kasu, S., Pallerla, M. K., Sai Ram, P., … Akella, V. (2004). Synthesis and structure-activity relationships of andrographolide analogues as novel cytotoxic agents. Bioorganic and Medicinal Chemistry Letters.

https://doi.org/10.1016/j.bmcl.2004.06.090

Patal, D. A., & Patal, D. J. (2018). Physicochemical characterization and in vitro dissolution enhancement of Mirabegron using solid dispersion method. World Journal of Pharmacy and Pharmaceutical Sciences7(5), 973–991.

Patel, K. V., Aspesi, A. V., & Evoy, K. E. (2015). Suvorexant. Annals of Pharmacotherapy49(4), 477–483.

https://doi.org/10.1177/1060028015570467

Rajani, M., Shrivastava, N., & Ravishankara, M. N. (2000). A rapid method for isolation of andrographolide from andrographis paniculata nees (kalmegh). Pharmaceutical Biology38(3), 204–9.

https://doi.org/10.1076/1388-0209(200007)3831-SFT204

Saha, S., Begum, R., Rahman, A., Sultan, M. Z., Amran, M. S., & Hossain, M. A. (2015). Evaluation of in vitro Interaction of Metformin with Ibuprofen in Aqueous Medium. Bangladesh Pharmaceutical Journal16(2), 189–194.

https://doi.org/10.3329/bpj.v16i2.22303

Saha, S., Begum, R., Sultan, M. Z., Amjad, F. M., Amran, M. S., & Hossain, M. A. (2013). In vitro Interaction of Metformin with Diclofenac in Aqueous Medium. Dhaka University Journal of Pharmaceutical Sciences11(2), 101–106.

https://doi.org/10.3329/dujps.v11i2.14555

Sajeeb, B., Kumar, U., Halder, S., & Bachar, S. C. (2015). Identification and Quantification of Andrographolide from Andrographis paniculata (Burm. f.) Wall. ex Nees by RP-HPLC Method and Standardization of its Market Preparations. Dhaka University Journal of Pharmaceutical Sciences14(1), 71–78.

https://doi.org/10.3329/dujps.v14i1.23738

Sultana, N., Arayne, M. S., Rizvi, S. B. S., Haroon, U., & Mesaik, M. A. (2013). Synthesis, spectroscopic, and biological evaluation of some levofloxacin metal complexes. Medicinal Chemistry Research.

https://doi.org/10.1007/s00044-012-0132-9

Sutton, E. L. (2015). Profile of suvorexant in the management of insomnia. Drug Design, Development and Therapy9, 6035–42.

https://doi.org/10.2147/DDDT.S73224

Takasu, T., Ukai, M., Sato, S., Matsui, T., Nagase, I., Maruyama, T., … Yamaguchi, O. (2007). Effect of (R)-2-(2-aminothiazol-4-yl)-4’-{2-[(2-hydroxy-2-phenylethyl)amino]ethyl} acetanilide (YM178), a novel selective beta3-adrenoceptor agonist, on bladder function. The Journal of Pharmacology and Experimental Therapeutics321(2), 642–7.

https://doi.org/10.1124/jpet.106.115840

Takusagawa, S., Miyashita, A., Iwatsubo, T., & Usui, T. (2012). In vitro inhibition and induction of human cytochrome P450 enzymes by mirabegron, a potent and selective β3-adrenoceptor agonist. Xenobiotica42(12), 1187–1196.

https://doi.org/10.3109/00498254.2012.700140

Teresa Carr. (2016). FDA Fields Complaints on Sleeping Pill Suvorexant. Consumer Reports.

Vasanthabharathi, V., & Jayalakshmi, S. (2018). Bioactive potential from Marine sponge Callyspongia diffusa associated Pseudomonus fluorescens BCPBMS-1 and Penicillum citrinum. Microbial Bioactives1(1), 8–13.

https://doi.org/10.25163/microbbioacts.11002A2221300318

WHO media center. (2007). WHO monographs on selected medicinal plants (Vol. 3). Geneve: World Health Organization. Retrieved from http://www.who.int/medicines/areas/traditional/

Wu, Y. S., Ngai, S. C., Goh, B. H., Chan, K. G., Lee, L. H., & Chuah, L. H. (2017). Anticancer activities of surfactin potential application of nanotechnology assisted surfactin delivery. Frontiers in Pharmacology8(OCT), 1–22.

https://doi.org/10.3389/fphar.2017.00761

PDF
Full Text
Export Citation

View Dimensions


View Plumx



View Altmetric



25
Save
0
Citation
1437
View
2
Share