Computational approach to explore the inhibitory potential of biologically derived compounds against Spodoptera litura vitellogenin receptor (VgR) using structure based virtual screening and molecular dynamics.

In the everlasting combat against the pests of agricultural importance, it is essential to come up with a novel strategy for pest control. This can be achieved through understanding the insect pest at cellular and molecular levels. Vitellogenin (Vg) and vitellogenin receptor (VgR) are essential for successful reproduction in insect. The N-terminal Ligand Binding Domain (LBD) of VgR is responsible for the transportation of vital protein (Vg) to the developing oocyte through receptor mediated endocytosis pathway. This can be implemented to various predicaments and betterments for exploitation in pest management, in a target specific and eco-friendly manner. For this, natural metabolites isolated from various biological sources were used as ligand. The purpose of this study was to analyze the inhibitory potential of 14 biologically derived compounds against N-terminal (Ligand Binding Repeats) LBRs of S. litura by computational docking. 3 D structure of LBRs of S. litura was generated by Raptor X software and the structure was refined and validated. The validated structure was docked using autodock vina. Docking results revealed that spinosyn A and milbemycin A4 have inhibitory activity against VgR. Molecular dynamics (MD) simulation confirms the stable binding of the ligand. From the above results, spinosyn A and milbemycin A4 may be exploited for the pest management.Communicated by Ramaswamy H. Sarma.

Evaluation of anti rheumatic activity of Piper betle L. (Betelvine) extract using in silico, in vitro and in vivo approaches.

Rheumatoid Arthritis is a chronic, inflammatory, and systemic autoimmune disease, it affects elders worldwide. Herbal medicines have been used for the treatment of various ailments from ancient times. Betelvine (Piper betle L.) leaves have long been used in Asian countries as a medicine to relieve pain and some metabolic diseases. The present study of methanolic extract of phytochemical analysis confirms the presence of alkaloids, tannins, terpenoids, saponins, steroids, total flavonoids and total phenols. GC-MS analysis of MeOH extract of Piper betle (PBME) revealed the presence of 40 bioactive compounds. In vitro antioxidant and anti-inflammatory assays showed greater inhibitory effect. The anti-arthritic effects of PBME at 250 and 500 mg/kg concentration showed recovery from joint damage in in vivo rat model. Among the 40 GC-MS derived bioactives, 4-Allyl-1,2-Diacetoxybenzene exhibited the higher interactions with minimized binding energy to the RA targets of MMP 1 (-6.4 kcal/mol), TGF-ß (-6.9 kcal/mol), IL-1ß (-5.9 kcal/mol). Further, the effect of PBME extract against RA molecular disease targets (IL-1ß, MMP1 and TGF- ß) were studied using Real-time PCR. These results substantiate that P. betle leaves could be a source of therapeutics for the treatment of rheumatoid arthritis.

Bioactive Metabolites from Marine Ascidians: Future Treatment for Autism Spectrum Disorder.

Autism spectrum disorder (ASD) is a developmental disorder that influences communication and behavior. Numerous researches propose that genes can act together with manipulations from the environment to affect development in ways that lead to ASD. The broad range of issues facing people with ASD means that there is no single proper drug and treatment for ASD. Numerous shortcomings associated with the present conventional therapeutic strategies have forced researchers to venture into alternative natural sources for effective compounds. The marine environment has emerged as an alternate search environment due to its versatile conditions where organisms employ various biodefense mechanisms for their survival. Ascidians are an excellent source for unique bioactive compounds with nutritive and therapeutic content and it still holds credit for being an underused source from marine animals. Bioactive compounds isolated from ascidians have various commendable biomedical applications due to their unique chemical structures. The present chapter will focus on the potential of bioactive compounds derived from ascidians for the treatment of the neurologic disorder-ASD.

Tunicates as a biocontrol tool for larvicides acute toxicity of Zika virus vector Aedes aegypti.

In this present study, we conducted untargeted metabolic profiling using gas chromatography-mass spectrometry (GC-MS) analysis of ascidian Didemnum bistratum to assess the chemical constituents by searching in NIST library with promising biological properties against anti-bacterial and Zika virus vector mosquitocidal properties. Metabolites, steroids and fatty acids are abundant in crude compounds of ascidian D. bistratum and showed potential zone growth inhibition against bacterial strains Kluyvera ascorbate (10 mm). The active crude compounds of D. bistratum exhibited prominent larvicidal activity against the Zika vector mosquitoes of Aedes aegypti (LC50 values of 0.44 mg/ml) and Cluex quinquefasciatus (LC50 values of 2.23 mg/ml). The findings of this study provide a first evidence of the biological properties exhibited by D. bistratum extracts, thus increasing the knowledge about the Zika virus vector mosquitocidal properties of ascidian. Overall, ascidian D. bistratum is promising and biocontrol or eco-friendly tool against A. aegypti and C. quinquefasciatus with prospective toxicity against non-target organisms.

Chemical diversity and anti-proliferative activity of marine algae.

The chemical diversity of three macroalgae (Ulva reticulata, Sargassum wightii, Gracilaria sp) were determined using the GC-MS method with principal component analysis (PCA) and their potential efficacy against human pathogens and cervical carcinoma cells evaluated using MTT bioassay method. Our results showed that >30 metabolites were detected in three seaweeds, among these, steroids and fatty acids are the most dominant chemical group that highly contributes to discriminate this species. The PCA of GC-MS mass spectral variables showed a clear discrimination between three different species based on the phytochemical diversity of seaweeds. The extracts of U. reticulata exhibited anti-microbial activity with Pseudomonas aeruginosa (6.00 mm) and showed potential anti-proliferative activity against the HeLa cells (IC50 37 µmol/L) at concentration 1-50 µM treatment. Results of this study concluded that PCA analysis of mass spectral variables could be utilized as a reliable tool for species discrimination and chemotaxonomic classification of seaweeds.

Patterns of chemical diversity in the marine ascidian Phallusia spp.: anti-tumor activity and metabolic pathway inhibiting steroid biosynthesis.

The complex nature of marine biodiversity is partially responsible for the lack of studies in Indian ascidian species, which often target a small number of novel biomolecules. We performed untargeted metabolomics using gas chromatography-mass spectrometry (GC-MS) in two invasive ascidian species to investigate the inter-specific chemical diversity of Phallusia nigra and P. arabica in search of drug-like properties and metabolic pathways. The chemical profiling of individual ascidian species was obtained using GC-MS, and the metabolites were determined by searching in NIST library and literature data. The principal component analysis of GC-MS mass spectral variables showed a clear discrimination of these two ascidian species based on the chemical composition and taxonomy. The metabolites, lipids, macrolides, and steroids contributed strongly to the discrimination of these two species. Results of this study confirmed that GC-MS-based chemical profiling could be utilized as a tool for chemotaxonomic classification of ascidian species. The extract of P. nigra showed promising anti-tumor activity against HT29 colon cancer 35 µM and MCF7-breast cancer (34.76 µM) cells compared to P. arabica. Of the more than 70 metabolites measured, 18 metabolites that mapped various pathways linked to three metabolic pathways being impacted and altered in steroid biosynthesis, primary bile acid biosynthesis, and steroid hormone biosynthesis were observed to have changed significantly (p > 0.004, FDR < 0.01). Also, higher expression of this pathway was associated with more significant cytotoxicity in breast and colon carcinoma cells.