Abstract
Diarylheptanoids are a major class of plant secondary metabolites characterized by 1, 7-diphenyl heptanes in a seven-member carbon frame. In the present study, diarylheptanoids (garuganins 1, 3, 4 and 5) isolated from Garuga pinnata stem bark were evaluated for cytotoxic activity against MCF-7 and HCT15 cancer cell lines. Among the tested compounds, garuganin 5 and 3 exhibited the highest cytotoxic activity against HCT15 and MCF-7 with IC50 2.9 ± 00.8 μg/mL, 3.3 ± 0.1 μg/mL and 3.2 ± 0.1 μg/mL, and 3.5 ± 0.3 μg/mL, respectively. The molecular docking of garuganin 1, 3, 4 and 5 exhibited significant affinity toward the tested EGFR 4Hjo protein. The free energy and inhibitory constant of the compounds ranged from − 7.47 to − 8.49 kcal/mol and 3.34 micromolar to 944.20 nM nanomolar, respectively. Based on the results of cytotoxic activity, garuganin 5 and 3 were further evaluated for time- and concentration-dependent intracellular accumulation studies. The time-dependent intracellular concentration of garuganin 3 and 5 after 5 h of incubation increased about 5.5- and 4.5-fold, 204.16 ± 0.02 and 145.4 ± 0.36 nmol/L mg, respectively. The concentration-dependent intracellular concentration of garuganin 3 and 5 at 200 µg/mL increased of about > 12- and ninefold, 186.22 ± 0.05 and 98.73 ± 0.02 nmol/L mg, respectively. The intracellular concentrations of garuganin 3 and 5, in the presence of verapamil, cyclosporine and MK 571, was found to be significant in the basal direction compared to the apical directions. The results indicate that, garuganin 3 and 5 exhibited significant cytotoxic activity against MCF-7 and HCT15 cancer cell lines and also exhibited high binding affinity toward EGFR protein compared to garuganin 1 and 4.
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Acknowledgements
The authors are grateful to the Chancellor, Chaitnya Deemed to be University, for his cooperation and encouragement and also thankful to the Department of Biotechnology, NIT Warangal, for providing facilities for this research work.
Funding
The research leading to these results received funding from the Science and Engineering Research Board (SERB), New Delhi, India, under the project of TARE (Teachers Associateship for Research Excellence). Grant. FILE NO.TAR/2018/000561.
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Konakanchi, S., Vadluri, R., Anumula, K.S. et al. Antiproliferative, molecular docking, and bioavailability studies of diarylheptanoids isolated from stem bark of Garuga pinnata Rox B.. 3 Biotech 13, 208 (2023). https://doi.org/10.1007/s13205-023-03581-4
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DOI: https://doi.org/10.1007/s13205-023-03581-4