Somya Asthana

Bio: Somya Asthana is an academic researcher from Indian Institute of Toxicology Research. The author has contributed to research in topics: Docking (molecular) & Receptor. The author has an hindex of 7, co-authored 16 publications receiving 131 citations. Previous affiliations of Somya Asthana include Council of Scientific and Industrial Research & National Institute of Technology, Rourkela.

Toxicity of Naturally Occurring Anthraquinones

Abstract: Among the vast array of secondary metabolites produced by plants, anthraquinones (AQs) are the group of compounds produced by different plants of various families such as Polygonaceae, Rhamnaceae, Rubiaceae, Fabaceae, Xanthorrhoeaceae, Leguminosae, and Liliacae. Owing to their biological and chemical diversity, AQs have wide industrial applications in food, pharmaceutical, and paper industries. Despite their diverse application, anthraquinones have been reported to be toxic to experimental animals. However, very little is known about their toxicity on the human population. In this chapter, the metabolic routes for the biosynthesis of AQs in plants have been described. Efforts have been focused on the profile of AQs present in different plant species and their toxic effects on the various animal models and in humans.

Molecular modeling and docking study to elucidate novel chikungunya virus nsP2 protease inhibitors

Abstract: Chikungunya is one of the tropical viral infections that severely affect the Asian and African countries. Absence of any suitable drugs or vaccines against Chikungunya virus till date makes it essential to identify and develop novel leads for the same. Recently, nsP2 cysteine protease has been classified as a crucial drug target to combat infections caused by Alphaviruses including Chikungunya virus due to its involvement viral replication. Here in, we investigated the structural aspects of the nsP2 protease through homology modeling based on nsP2 protease from Venezuelan equine encephalitis virus. Further, the ligands were virtually screened based on various pharmacological, ADME/Tox filters and subjected to docking with the modeled Chikungunya nsP2 protease using AutoDock4.2. The interaction profiling of ligand with the protein was carried out using LigPlot(+). The results demonstrated that the ligand with PubChem Id (CID_5808891) possessed highest binding affinity towards Chikungunya nsP2 protease with a good interaction profile with the active site residues. We hereby propose that these compounds could inhibit the nsP2 protease by binding to its active site. Moreover, they may provide structural scaffold for the design of novel leads with better efficacy and specificity for the nsP2 protease.

Interaction of anthraquinones of Cassia occidentalis seeds with DNA and Glutathione.

Abstract: Consumption of Cassia occidentalis (CO) seeds has been associated with the hepatomyoencephalopathy (HME) in children. Recently, we have characterized the toxic anthraquinones (AQs) such as Emodin, Rhein, Aloe-emodin, Chrysophanol and Physcion in CO seeds and detected these moieties in the bio fluids of CO poisoning cases. As AQs were detected in the serum of HME patients, their interaction with key biomolecules including protein, DNA and glutathione (GSH) is imperative. In this regard, we have previously reported the interaction of these AQs with serum albumin protein and their subsequent biological effects. However, the interaction of these AQs with DNA and GSH remained unexplored. In the present work, we have studied the binding of these AQs of CO seeds with DNA and GSH by fluorescence spectroscopy, UV–vis spectral analysis, molecular docking, and biochemical studies. Results indicated a higher binding affinity for Emodin (Ka = 3.854 × 104 L mol−1 S−1), Aloe-emodin (Ka = 0.961 × 104 L mol−1 S−1) and Rhein (Ka = 0.034 × 104 L mol−1 S−1) towards calf thymus DNA may be associated with their higher cytotoxicity. Alternatively, Physcion and Chrysophanol which showed less cytotoxicity in our earlier studies exhibited very low DNA binding. The binding pattern of all these AQs is consistent with the in-silico data. Absorption spectroscopy studies indicated the possible formation of GSH conjugate with Aloe-emodin and Physcion. Further biochemical measurement of GSH and GSSG (Glutathione disulfide) following incubation with AQs indicated that Aloe-emodin (28%) and Rhein (30%) oxidizes GSH to GSSG more as compared to other AQs. Taken together, these results suggest that the higher cytotoxicity of Rhein, Emodin and Aloe-emodin may be attributed to their potent DNA and GSH binding affinity.

Molecular Docking and Interactions of Pueraria Tuberosa with Vascular Endothelial Growth Factor Receptors.

Abstract: Pueraria tuberosa is known for its therapeutic potentials in cardiovascular disorders, but its effect in angiogenesis has not been studied so far. In this study, a computational approach has been applied to elucidate the role of the phytochemicals in inhibition of angiogenesis through modulation of vascular endothelial growth factor receptors: Vascular endothelial growth factor receptor-1 and vascular endothelial growth factor receptor-2, major factors responsible for angiogenesis. Metabolite structures retrieved from PubChem and KNApSAcK - 3D databases, were docked using AutoDock4.2 tool. Hydrogen bond and molecular docking, absorption, distribution, metabolism and excretion and toxicity predictions were carried out using UCSF Chimera, LigPlot(+) and PreADMET server, respectively. From the docking analysis, it was observed that puerarone and tuberostan had significant binding affinity for the intracellular kinase domain of vascular endothelial growth factor receptors-1 and vascular endothelial growth factor receptor-2 respectively. It is important to mention that both the phytochemicals shared similar interaction profile as that of standard inhibitors of vascular endothelial growth factor receptors. Also, both puerarone and tuberostan interacted with Lys861/Lys868 (adenosine 5'-triphosphate binding site of vascular endothelial growth factor receptors-1/vascular endothelial growth factor receptors-2), thus providing a clue that they may enforce their inhibitory effect by blocking the adenosine 5'-triphosphate binding domain of vascular endothelial growth factor receptors. Moreover, these molecules exhibited good drug-likeness, absorption, distribution, metabolism and excretion properties without any carcinogenic and toxic effects. The interaction pattern of the puerarone and tuberostan may provide a hint for a novel drug design for vascular endothelial growth factor tyrosine kinase receptors with better specificity to treat angiogenic disorders.

Aloe‐emodin: A review of its pharmacology, toxicity, and pharmacokinetics

Abstract: Emodin is a natural anthraquinone derivative that occurs in many widely used Chinese medicinal herbs, such as Rheum palmatum, Polygonum cuspidatum and Polygonum multiflorum Emodin has been used as a traditional Chinese medicine for over 2000 years and is still present in various herbal preparations Emerging evidence indicates that emodin possesses a wide spectrum of pharmacological properties, including anticancer, hepatoprotective, antiinflammatory, antioxidant and antimicrobial activities However, emodin could also lead to hepatotoxicity, kidney toxicity and reproductive toxicity, particularly in high doses and with long-term use Pharmacokinetic studies have demonstrated that emodin has poor oral bioavailability in rats because of its extensive glucuronidation This review aims to comprehensively summarize the pharmacology, toxicity and pharmacokinetics of emodin reported to date with an emphasis on its biological properties and mechanisms of action Copyright © 2016 John Wiley & Sons, Ltd

Screening of ferulic acid related compounds as inhibitors of xanthine oxidase and cyclooxygenase-2 with anti-inflammatory activity

Abstract: The ferulic and gallic acid related compounds from natural origin were studied against xanthine oxidase and cyclooxygenase-2 along with their anti-inflammatory activity. The compounds gallic acid, ferulic acid, caffeic acid and p-coumaric acid revealed promising anti-inflammatory activity (30–40% TNF-α and 60–75% IL-6 inhibitory activity at 10 µM). Bioavailability of compounds were checked by in vitro cytotoxicity using CCK-8 cell lines and confirmed to be nontoxic, but found toxic at higher concentration (50 µM). Gallic, ferulic, caffeic acid was demonstrated potential dual inhibition toward xanthine oxidase and cyclooxygenase-2 as calculated by IC50: 68, 70.2, and 65 µg/ml (xanthine oxidase) and 68.5, 65.2, and 62.5 µg/ml (cyclooxygenase-2), respectively. The structure activity relationship and in silico drug relevant properties (HBD, HBA, PSA, c Log P, ionization potential, molecular weight, EHOMO and ELUMO) further confirmed that the compounds were potential candidates for future drug discovery study, which was expected for further rational drug design against xanthine oxidase and cyclooxygenase.