Binding and molecular dynamic studies of sesquiterpenes (2R-acetoxymethyl-1,3,3-trimethyl-4t-(3-methyl-2-buten-1-yl)-1t-cyclohexanol) derived from marine Streptomyces sp. VITJS8 as potential anticancer agent

Abstract

The main aim of the current study is to explore the bioactive potential of Streptomyces sp. VITJS8 isolated from the marine saltern. The cultural, biochemical, and morphological studies were performed to acquire the characteristic features of the potent isolate VITJS8. The 16Sr DNA sequencing was performed to investigate the phylogenetic relationship between the Streptomyces genera. The structure of the compound was elucidated by gas chromatography-mass spectrometry (GC-MS), infra-red (IR), and ultra-violet (UV) spectroscopic data analysis. The GC-MS showed the retention time at 22.39 with a single peak indicating the purity of the active compound, and the molecular formula was established as C14H9ONCl2 based on the peak at m/z 277 [M](+). Furthermore, separated by high-performance liquid chromatography (HPLC), their retention time (t r) 2.761 was observed with the absorption maxima at 310 nm. The active compound showed effective inhibitory potential against four clinical pathogens at 500 μg/mL. The antioxidant activity was found effective at the IC50 value of 500 μg/mL with 90 % inhibition. The 3-(4,5-dimethylthiazol-2-yl)-2,5-ditetrazolium bromide (MTT) assay revealed the cytotoxicity against HepG2 cells at IC50 of 250 μg/mL. The progression of apoptosis was evidenced by morphological changes by nuclear staining. The DNA fragmentation pattern was observed at 250 μg/mL concentration. Based on flow cytometric analysis, it was evident that the compound was effective in inhibiting the sub-G0/G1 phase of cell cycle. The in vitro findings were also supported by the binding mode molecular docking studies. The active compound revealed minimum binding energy of -7.84 and showed good affinity towards the active region of topoisomerase-2α that could be considered as a suitable inhibitor. Lastly, we performed 30 ns molecular dynamic simulation analysis using GROMACS to aid in better designing of anticancer drugs. Simulation result of root mean square deviation (RMSD) analysis showed that protein-ligand complex reaches equilibration state around 10 ns that illustrates the docked complex is stable. We propose the possible mechanism of sesquiterpenes to play a significant role in antitumor cascade. Hence, our studies open up a new facet for a potent drug as an anticancer agent.

Prostaglandins Isolated from the Octocoral Plexaura homomalla: In Silico and In Vitro Studies Against Different Enzymes of Cancer

“…In addition, it was observed that most of the H-bonds were formed with Gly 164 , Asn 150 , Asn 120 , Ala 167 , Thr 215 , and Ser 149 residues, which are part of the enzyme binding site. Similar interactions were observed by Jemimah Naine et al [21] in their study.…”

Downregulation of RPN2 induces apoptosis and inhibits migration and invasion in colon carcinoma

“…Cell proliferation and apoptosis is a process of dynamic equilibration ( 25 ). Apoptosis suppression drive cells to escape death and leads to cell abnormal proliferation, further causing the occurrence and development of tumors ( 26 , 27 ).…”

Comparative GC-MS Analysis of Bioactive Phytochemicals from Different Plant Parts and Callus of Leptadenia reticulata Wight and Arn.

“…53 2R-Acetoxymethyl-1,3,3-trimethyl-4t-(3-methyl-2-buten-1-yl)-1t-cyclohexanol was present in highest amount in EALE (13.36%) and traces in MRE. It is a sesquiterpenoid and acts as an anticancer 54 and potent anti-inflammatory agent. 55 Pristane or 2,6,10,14-tetramethyl-Pentadecane was found only in EARE (1.08%).…”