Plant-Based Bioactive Phthalates Derived from Hibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

Farah Yasmin; Zill-I-Huma Nazli; Nusrat Shafiq; Maryam Aslam; Yousef A Bin Jardan; Hiba-Allah Nafidi; Mohammed Bourhia

doi:10.1021/acsomega.3c03342

Plant-Based Bioactive Phthalates Derived from Hibiscus rosa-sinensis: As In Vitro and In Silico Enzyme Inhibition

ACS Omega. 2023 Aug 28;8(36):32677-32689. doi: 10.1021/acsomega.3c03342. eCollection 2023 Sep 12.

Authors

Farah Yasmin¹, Zill-I-Huma Nazli², Nusrat Shafiq¹, Maryam Aslam³, Yousef A Bin Jardan⁴, Hiba-Allah Nafidi⁵, Mohammed Bourhia⁶

Affiliations

¹ Synthetic and Natural Products Discovery (SNPD) Laboratory, Department of Chemistry, Government College Women University Faisalabad 38000, Pakistan.
² Department of Chemistry, Government College Women University, Faisalabad 38000, Pakistan.
³ Green Chemistry Laboratory, Department of Chemistry, Government College Women University, Faisalabad 38000, Pakistan.
⁴ Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box, Riyadh 11451, Saudi Arabia.
⁵ Department of Food Science, Faculty of Agricultural and Food Sciences, Laval University, Quebec City G1 V 0A6, Quebec, Canada.
⁶ Department of Chemistry and Biochemistry, Faculty of Medicine and Pharmacy, Ibn Zohr University, Laayoune 70000, Morocco.

Abstract

Hibiscus rosa-sinensis is an attractive, ever-blossoming, and effortlessly available plant around the globe. The fabulous flowers of H. rosa-sinensis enjoy a significant status in folk medicine throughout the world and comprise a range of phyto constituents due to which this splendid flower owns numerous biological and pharmaceutical activities like antioxidant, antifungal, antimicrobial, anti-inflammatory, antipyretic, antidiabetic, and antifertility activity. Considering this, column chromatographic isolation of the phytoconstituents of ethyl acetate fraction of the flowers of H. rosa-sinensis was performed. A series of five phthalates including Di-n-octyl phthalate (HR1), ditridecyl phthalate (HR2), 1-allyl 2-ethyl phthalate (HR3), diethyl phthalate (HR4), and bis (6-methylheptyl) phthalate (HR5) were isolated. The structures of the isolated phthalates were elucidated by gas chromatography-mass spectrometry, ¹H NMR, and ¹³C NMR. In silico and in vitro antidiabetic and antioxidant potential and DFT studies of isolated phthalates were carried out. In our study, isolated ligands were explored as potent antidiabetic as well as antioxidant agents as they exhibited good binding affinity (in in vitro and in silico experiments) against all selected protein targets. Compounds HR1-HR5 showed that the binding affinity value ranged from -5.9 to -5.2 kcal/mol, -5.5 to -4.3 kcal/mol, and -5.0 to -4.1 kcal/mol for target proteins 1HNY, 2I3Y, and 5O40, respectively. Among all isolated phthalates, HR5 can be a lead compound as it showed the best binding affinity with human pancreatic α-amylase (ΔG = -5.9 kcal/mol) and displayed a minimum inhibition concentration (IC₅₀) of 11.69 μM among all phthalates. Compound HR1 was the best docked and scored compound for inhibiting glutathione peroxidase; however, HR2 possessed the lowest binding score of -5.0 kcal/mol, thus indicating the highest potential among isolated phthalates for inhibiting the superoxide dismutase. Furthermore, the top-ranked docked ligand-protein complex for each protein was assessed for stability of protein and complex mobility by molecular dynamics simulation using the IMOD server.