Dataset Information

Cytotoxicity and molecular docking analysis of racemolactone I, a new sesquiterpene lactone isolated from Inula racemosa.

ABSTRACT:

Context

Traditionally, Inula racemosa Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds.

Objective

To isolate and characterize new cytotoxic phytoconstituents from I. racemosa roots.

Materials and methods

The column chromatography of I. racemosa ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/2D), ES-MS and its cytotoxic properties were assessed on HeLa, MDAMB-231, and A549 cell lines using MTT and LDH (lactate dehydrogenase) assays. Further, morphological changes were analyzed by flow cytometry, mitochondrial membrane potential, AO-EtBr dual staining, and comet assay. Molecular docking and simulation were performed using Glide and Desmond softwares, respectively, to validate the mechanism of action.

Results

The isolated compound was identified as racemolactone I (compound 1). Amongst the cell lines tested, considerable changes were observed in HeLa cells. Compound 1 (IC₅₀ = 0.9 µg/mL) significantly decreased cell viability (82%) concomitantly with high LDH release (76%) at 15 µg/mL. Diverse morphological alterations along with significant increase (9.23%) in apoptotic cells and decrease in viable cells were observed. AO-EtBr dual staining also confirmed the presence of 20% apoptotic cells. A gradual decrease in mitochondrial membrane potential was observed. HeLa cells showed significantly increased comet tail length (48.4 µm), indicating broken DNA strands. In silico studies exhibited that compound 1 binds to the active site of Polo-like kinase-1 and forms a stable complex.

Conclusions

Racemolactone I was identified as potential anticancer agent, which can further be confirmed by in vivo investigations.

SUBMITTER: Alam P

PROVIDER: S-EPMC8274518 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Publications

Cytotoxicity and molecular docking analysis of racemolactone I, a new sesquiterpene lactone isolated from <i>Inula racemosa</i>.

Alam Perwez P Tyagi Rama R Farah Mohammad Abul MA Rehman Md Tabish MT Hussain Afzal A AlAjmi Mohamed Fahad MF Siddiqui Nasir Ali NA Al-Anazi Khalid Mashay KM Amin Saima S Mujeeb Mohd M Mir Showkat R SR

Pharmaceutical biology 20211201 1

<h4>Context</h4>Traditionally, <i>Inula racemosa</i> Hook. f. (Asteraceae) has been reported to be effective in cancer treatment which motivated the authors to explore the plant for novel anticancer compounds.<h4>Objective</h4>To isolate and characterize new cytotoxic phytoconstituents from <i>I. racemosa</i> roots.<h4>Materials and methods</h4>The column chromatography of <i>I. racemosa</i> ethyl acetate extract furnished a novel sesquiterpene lactone whose structure was established by NMR (1D/ ...[more]

PMID: 35294328

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