The cytotoxic, antioxidant, and anticholinesterase activity of steviol and isosteviol analogues, together with structure-activity relationships and molecular docking studies
Wisal A. Ullah A. Khan B. Sıcak Y. Öztürk M. Muhammad A. Anwar W. Begum S. Zafar S. Carvalho P.V. Hassan S.S. Halim S.A. Khan A.
15 November 2025Elsevier B.V.
Journal of Molecular Structure
2025#1345
This study investigates the cytotoxic, antioxidant, and anticholinesterase activities of compounds derived from steviol and isosteviol. The cytotoxic activity of compounds (2f, 3e, 3h, 3k, 3l, and 3m) was determined using the MTT assay. Moreover, in vivo cytotoxicity/neurotoxicity of compounds was also performed on male albino mice as an experimental animal model. The derivatives showed good cytotoxicity against glioblastoma MG-U87 cancerous cell lines compared to the positive control, Cisplatin. In addition, D-Gal significantly increased the expression of p-NF-kB by the apoptotic protein markers in adult male albino mice. Compounds 3h and 2f were found to be very safe, while compound 2f exhibited better cytotoxicity (IC50 value 188 µM), thus may be considered as a lead molecule to develop new anticancer agents. The antioxidant and anticholinesterase activities of compounds (2b, 2d, 2e, 2f, 3d, and 3i) were evaluated, where all the compounds (except 2b) exhibited significant antioxidant activity. Compound 3d demonstrated the highest activity in ABTS (IC50: 284.6 µM) and CUPRAC (TEAC: 763.8 ± 35.23 µg/mg compound) assays, while 2e exhibited the highest metal chelating activity (IC50: 360.8 µM). Compound 2i showed moderate DPPH scavenging activity (IC50: 452.6 µM) and good butyrylcholinesterase (BChE) inhibitory activity (IC50: 144.4 µM). The results suggested that the compounds 2i, 3d, 3i, and 2b had antioxidant and anticholinesterase potentials. Additionally, molecular docking into the active sites of AChE, BChE, and PI3K enzymes deduced the binding modes of active compounds in their respective targets, and the docking results correlate well with the experimental outcomes. Therefore, these compounds could be considered as functional food ingredients and nutraceuticals. The structure-activity relationships for all activities are also discussed herein. Overall, the study advances our knowledge of the anticancer and antioxidant activity of steviol and isosteviol-derived compounds and their potential as lead candidates for future therapeutic development in cancer and Alzheimers disease.
17,16-Dihydroxy isosteviol , 4-Nitrophenyl hydrazone , Anticancer , Antioxidant activity , Isosteviol , Metal chelating activity , Steviol
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Department of Chemistry, Islamia College Peshawar, KP, Peshawar, 25000, Pakistan
Mugla Sitki Kocman University, Koycegiz Vocational School, Muğla, Köyceğiz, 48800, Turkey
Mugla Sitki Kocman University, Faculty of Sciences, Department of Chemistry, Muğla, Kötekli, 48121, Turkey
Al-Farabi Kazakh National University, Faculty of Chemistry and Chemical Technology, Almaty, Kazakhstan
Department of Pulmonology, Rehman Medical Institute, KP, Peshawar, 25000, Pakistan
Institute of Chemical Sciences, University of Peshawar, Peshawar, 25120, Pakistan
Centre for Technological Development in Health (CDTS), Oswaldo Cruz Foundation (FIOCRUZ), Building Expansão, 8th floor room 814, Av. Brasil 4036-Manguinhos, RJ, Rio de Janeiro, 21040-361, Brazil
Jamil–ur–Rahman Center for Genome Research, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan
Natural and Medical Sciences Research Centre, University of Nizwa, 616 Birkat Al-Mauz, Nizwa, PO Box 33, Oman
Department of Chemical and Biological Engineering, College of Engineering, Korea University, Seoul, 02841, South Korea
Department of Chemistry
Mugla Sitki Kocman University
Mugla Sitki Kocman University
Al-Farabi Kazakh National University
Department of Pulmonology
Institute of Chemical Sciences
Centre for Technological Development in Health (CDTS)
Jamil–ur–Rahman Center for Genome Research
Natural and Medical Sciences Research Centre
Department of Chemical and Biological Engineering
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