A New Cytotoxic Dimeric Sesquiterpene Isolated from <i>Inula racemosa</i> Hook. f. (Root): <i>In Vitro</i> and <i>In Silico</i> Analyses

• Main Authors: Rama Tyagi, Perwez Alam, Md. Tabish Rehman, Mohamed Fahad AlAjmi, Afzal Hussain, Saima Amin, Mohd. Mujeeb, Showkat R. Mir
• Format: Article
• Language: English
• Published: MDPI AG 2021-12-01
• Series: Separations
• Subjects: <i>Inula racemosa</i>; dimeric sesquiterpene; disesquicin; cytotoxicity; molecular docking; simulation
• Online Access: https://www.mdpi.com/2297-8739/8/1/2
• ISSN: 2297-8739

A new dimeric sesquiterpene named disesquicin (compound <b>1</b>) was isolated from <i>Inula racemosa</i> roots by normal-phase MPLC (Medium Pressure Liquid Chromatography), and its structure was established by using extensive spectral analysis. Compound <b>1,</b> when tested on different human cancer cell lines, showed marked cytotoxic activity (IC₅₀ (µg/mL): 5.99 (MDA-MB), 9.10 (HeLa), and 12.47 (A549)). Docking study revealed that it binds at the catalytic domain of PLK-1 and interacts with catalytic site residues Leu59, Gly60, Lys61, Gly62, Cys67, Ala80, Lys82, Leu130, Arg136, Ser137, Leu139, Glu140, Lys178, Gly180, Asn181, Phe183, and Asp194. The binding of compound <b>1</b> to PLK-1 is spontaneous in nature as evident by a free energy of—8.930 kcal mol⁻¹, corresponding to a binding affinity of 3.54 × 10⁶M⁻¹. Results showed that compound <b>1 </b>exhibited cytotoxic potential that was further confirmed by in vivo investigations.