Receptor based virtual screening of potential novel inhibitors of tigar [TP53 (tumour protein 53)-induced glycolysis and apoptosis regulator.

TP53 (tumor protein 53)-induced glycolysis and apoptosis regulator (TIGAR) belongs to the phosphatases family of proteins that modulates the level of reactive oxygen species in tumor cells. This protein plays a vital role as a negative regulator of glycolysis, thus lowering ROS levels in the cells, which helps the cancerous cells to resist programmed cell death. Besides, TIGAR also mediates the DNA damage repair in cancer cells by increasing tumor cell survival. In the current study, we have screened natural products that compete with the substrate to bind to the active site of TIGAR. Extra precision and MMGBSA scoring function were used to screen the lead molecules. Five compounds were considered as lead molecules with 2-(2-(3,4-dihydroxy phenyl)-3,5-dihydroxy-8-(4-hydroxyphenyl)-4-oxo-4H-furo[2,3-h]chromen-9-yl) acetic acid(DDFA) as a top lead with a docking score of -9.428, and -53.16 MMGBSA, bind to the positively charged amino acids present in the active site. Further, the molecular dynamics simulation studies indicated the structural stability attained by TIGAR protein upon the binding of DDFA, suggesting it to be a potent inhibitor of TIGAR, and could be employed as an anticancer drug during combinational therapy.

Caesalpinia Crista Linn. Induces Protection against DNA and Membrane Damage.

BACKGROUND: Caesalpinia crista is a medicinal herb used to cure various ailments in subtropical and tropical regions of Southeast Asia. OBJECTIVE: The objective of this evaluation of C. crista against free radical induced DNA and erythrocyte damage. MATERIALS AND METHODS: The profiles of polyphenol and flavonoid were quantified through reversed-phase high-performance liquid chromatography. Free radical induced DNA and membrane damage were performed using H2O2 as oxidative agent. RESULTS: The total polyphenol content of C. crista leaf ethyl acetate extract (CcEA) was 94.5 ± 3.8 mg/gGAE, CcME (C. crista leaf methanol extract) was 52.7 ± 2.8 mg/gGAE, and CcWE (C. crista leaf Water extract) was 31.84 ± 1.8 mg/gGAE. Total flavonoid content of CcEA was 60.46 ± 2.3 mg/gQE, CcME was 46.26 ± 1.8 mg/gQE, and CcWE was 20.47 ± 1.1 mg/gQE. The extracts also exhibited good antioxidant activity as confirmed by 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid), hydroxyl scavenging, reducing power, and total antioxidant assays. Among the three extracts, CcEA and CcME showed better protection against red blood cell (RBC) hemolysis and DNA damage as confirmed by electrophoretic study. Further, Scanning electron micrograph data showed that CcEA revealed the free radical induced structural alterations in RBC. CONCLUSION: These findings suggest that C. crista contains bioactive molecules and can inhibit oxidative stress and can be source of further study to use this in herbal medicine. SUMMARY: ROS are generated under normal biological systems. These ROS generated can be scavenged by endogenous and exogenous cellular mechanisms. Environmental stress, radiation, smoke etc. elevates ROS dramatically. This leads to significant damage to cellular biomolecules like DNA and cell structures. Plants as a large reservoir of drugs for protecting DNA and cell structures from oxidative stress. Polyphenols present in the C. crista extracts acts through several mechanisms to quench free radicals. Extracts exhibited potent antioxidant properties and also protected DNA and cell membrane from oxidative damage. Hence this can be used in herbal medicine for treating oxidative stress mediated diseases. Abbreviations used: ABTS: 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid); CcEA: C. crista leaf ethyl acetate extract; CcME: C. crista leaf methanol extract; CcWE: C. crista leaf Water extract; DPPH: 2,2-diphenyl-1-picrylhydrazyl; GAE: Gallic acid Equivalent; H2O2: Hydrogen Peroxide; QE: Quercetin Equivalent; RNS: Reactive Nitrogen Spevcies; ROS: Reactive Oxygen Species; SEM: Scanning Electron Microscope.

Sequence Analysis and Phylogenetic Studies of Hypoxia-Inducible Factor-1α.

Hypoxia-inducible factors (HIF) belong to the basic helix loop helix-PER ARNT SIM (bHLH-PAS) family of transcription factors that induce metabolic reprogramming under hypoxic condition. The phylogenetic studies of hypoxia-inducible factor-1α (HIF-1α) sequences across different organisms/species may leave a clue on the evolutionary relationships and its probable correlation to tumorigenesis and adaptation to low oxygen environments. In this study, we have aimed at the evolutionary investigation of the protein HIF-1α across different species to decipher their sequence variations/mutations and look into the probable causes and abnormal behaviour of this molecule under exotic conditions. In total, 16 homologous sequences for HIF-1α were retrieved from the National Center for Biotechnology Information. Sequence identity was performed using the Needle program. Multiple aligned sequences were used to construct the phylogeny using the neighbour-joining method. Most of the changes were observed in oxygen-dependent degradation domain and inhibitory domain. Sixteen sequences were clustered into 5 groups. The phylogenetic analysis clearly highlighted the variations that were observed at the sequence level. Comparisons of the HIF-1α sequence among cancer-prone and cancer-resistant animals enable us to find out the probable clues towards potential risk factors in the development of cancer.

Biofabrication of gold nanoparticles using marine endophytic fungus - Penicillium citrinum.

Nanotechnology is one of the promising fields of research and generating new avenues and applications in medicine. Recently, marine floras such as, marine endophytes are gaining the attention of many researchers due to the myriad of bioactive molecules that they possess. In addition, they find applications in many pharmaceutical and cosmetic industries. In this study, they have studied the green synthesis of gold nanoparticles (AuNPs) from Penicillium citrinum (P. citrinum) and its antioxidant activity. P. citrinum was isolated from brown algae. The identity of the fungus was established by comparing its 18S rDNA sequence. AuNPs were synthesised using P. citrinum and were characterised by UV-visible spectrophotometer (UV-vis), field emission scanning electron microscope (FESEM), X-ray diffraction, Fourier transform infrared spectroscopy and dynamic light scattering (DLS). AuNPs were tested for free radical scavenging activity by 1,1-diphenyl-2-picrylhydrazyl method. The particle sizes of AuNps were determined by FESEM and DLS. The reduction of gold metal ion was confirmed from the UV-vis spectrum. AuNPs showed significant antioxidant potential and the activity was comparable to the standard ascorbic acid. Further, in vitro and in vivo studies on these AuNPs will help in developing an alternative, cost-effective and acceptable drug for various ailments.

Antiangiogenic, wound healing and antioxidant activity of Cladosporium cladosporioides (Endophytic Fungus) isolated from seaweed (Sargassum wightii).

Endophytic fungi from marine seaweeds are the less studied group of organisms with vast medical applications. The aim of the present study was to evaluate antioxidant, antiangiogenic as well as wound healing potential of the endophytic fungus isolated from the seaweed Sargassum wightii. The morphological characters and the rDNA internal transcribed spacer sequence analysis (BLAST search in Gen Bank database) was used for the identification of endophytic fungus. The antioxidant potential of the ethyl acetate extract of endophytic fungus was assessed by, 1,1-diphenyl-2-picryl-hydrazyl radical scavenging method. The fungal extract was also analysed for reducing power, total phenolic and flavonoid content. Antiangiogenic activity of the fungal extract was studied in vitro by inhibition of wound healing scratch assay and in vivo by Chick chorioallantoic membrane assay. The endophytic fungus was identified as Cladosporium cladosporioides (Gen Bank ID - KT384175). The ethyl acetate extract of C. cladosporioides showed a significant antioxidant and angiosuppressive activity. The ESI-LC-MS analysis of the extract revealed the presence of wide range of secondary metabolites. Results suggest that C. cladosporioides extract could be exploited as a potential source for angiogenic modulators.