Microbial Bioactives
Microbial Bioactives | Online ISSN 2209-2161
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Volume 2 Number 1 2019
RESEARCH ARTICLE (Open Access)
Complexation of Andrographolide, Mirabegron and Suvorexant and Bioactivity Study of the Complexes
Rajia Sultana and Md. Zakir Sultana*
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: The development of novel bioactive compounds through drug–drug interaction and complexation has emerged as an alternative strategy to enhance therapeutic efficacy while potentially reducing unwanted side effects. In addition to their established pharmacological uses, certain bioactive molecules such as andrographolide have also been reported to possess antibacterial and broader biological activities, making them attractive candidates for the design of multifunctional therapeutic complexes. In this context, the present study explored whether selected small-molecule drugs could form new physicochemically distinct complexes with enhanced biological activity.
Methods: Three new drug complexes were prepared by solid-state drug–drug complexation using calculated w/w ratios of the precursor compounds. Equal amounts of drug pairs were mixed thoroughly using pestle and mortar, incubated at 50 °C for 4 h, and then kept at room temperature overnight to facilitate complex formation. The resulting complexes were characterized by Differential Scanning Calorimetry (DSC) and Fourier-transform infrared spectroscopy (FTIR). Their biological activity was further assessed using a HeLa cell line cytotoxicity assay.
Results: Distinct thermal transitions were observed for the newly formed complexes, indicating physicochemical interaction between the precursor drugs. The melting endothermic peaks of andrographolide–suvorexant, andrographolide–mirabegron, and suvorexant–mirabegron complexes were found at 221.02 °C, 189.49 °C, and 115.78 °C, respectively, compared with 230.87 °C, 127.09 °C, and 140.40 °C for andrographolide, suvorexant, and mirabegron alone. FTIR spectra retained the characteristic functional group signatures of the parent molecules while supporting intermolecular interaction within the complexes. Biologically, the newly formed complexes demonstrated enhanced cytotoxicity against HeLa cells, with more than 90% cell death, representing approximately 10% greater cytotoxic effect than the precursor compounds.
Conclusion: The findings indicate that drug–drug complexation can generate new bioactive molecular entities with altered physicochemical properties and enhanced cytotoxic potential. Given the previously reported broad biological relevance of certain precursor compounds, particularly andrographolide, these newly formed complexes may warrant further investigation not only for anticancer applications but also for broader bioactivity-guided therapeutic screening, including possible antimicrobial or antifungal relevance in future studies.
Keywords: Drug–drug complexation; Bioactive compounds; Cytotoxicity; Differential scanning calorimetry; Fourier-transform infrared spectroscopy; Andrographolide; Suvorexant; Mirabegron, Broad-spectrum bioactivity, Antimicrobial relevance, Drug repurposing
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