Molecular docking and in vitro antibacterial activity of chiral phthalimide on ESBL producing gram negative bacteria.

Antibiotic resistance is tricky enemy that challenges our healthcare system. It is a stealthy, adaptive and ever evolving opponent, which can take years to develop but can spread like wildfire. In this study, derivatives of chiral phthalimides were developed with this aim to control the growth of resistant strains of Klebsiella pneumonia, Escherichia coli and Pseudomonas aeruginosa by targeting their resistance causing proteins and explore their binding interaction focal points through computational docking. Total 8 novel chiral phthalimides were synthesized and its antibiogram analysis was done on Muller-Hinton Agar by disc diffusion method. Cytotoxicity studies were made to check efficacy of tested compounds on human RBCs and monitor release of hemoglobin absorbance at 540nm. By using in silico molecular approach, crystal structure of target protein was retrieved from Protein Data Bank and docked through Autodock vina and PyRx. The obtained results revealed that seven out of eight compounds have active inhibitory effects against virulent strains. Minimum Inhibitory Concentration (MIC) was measured for most potent compounds i.e., 2-(1,3-dioxoisoindolin-2-yl)-3-(4-hydroxyphenyl) propanoic acid (compound 7) and 3-(1,3-dioxoisoindolin-2-yl) propanoic acid (compound 8). Docking studies displayed a report of highest affinity binding points i.e., amino acids LYS315, ALA318, TYR150, THR262, HIS314 and ARG148 for compound 7 while ALA 318, LYS 315, ARG14 and ILE291 for compound 8.

Investigation of in vivo anti-inflammatory and anti-angiogenic attributes of coumarin-rich ethanolic extract of Melilotus indicus.

Inflammation and angiogenesis are two major contributors to tumourigenesis. Melilotus indicus is traditionally used as an anti-inflammatory agent. The current study was designed to investigate the anti-inflammatory and anti-angiogenic properties of ethanolic extract of M. indicus (Miet) whole plant and its marker compound (coumarin) using a series of in vivo methods. Extraction by maceration was adopted to prepare ethanolic extract. Phytochemical compounds present in Miet were investigated using both qualitative and quantitative methods. In vivo safety profile of Miet was investigated in behavioural studies. Four acute oedema models such as carrageenan, serotonin, histamine-induced paw oedema and xylene-induced ear oedema, and chronic formaldehyde-induced paw oedema model were employed to explore the anti-inflammatory potential of Miet. Chorioallantoic chick membrane assay (CAM) was performed to explore anti-angiogenic potential of Miet. Histopathological evaluations were conducted to access improvement in skin texture of paws. TNF-α ELISA kit was used to study effects of treatment on serum levels of TNF-α. Extraction by maceration resulted in formation of greenish coloured semisolid extract with a high coumarin content. In vivo toxicological studies revealed LD50 of Miet was greater than 8000 mg/kg. Data of acute inflammatory models depicted significant (p < 0.05) inhibition of oedema in Miet, coumarin and standard (piroxicam/indomethacin) treated groups. 750 mg/kg of Miet induced comparable (p > 0.05) anti-inflammatory effects to that of standard-treated groups. Coumarin showed better anti-inflammatory effects in carrageenan-induced paw oedema model as compared with histamine- and serotonin-induced oedema models. Data of chronic inflammatory models also depicted dose-dependent anti-inflammatory attributes of Miet which were comparable with standard treated groups. Significant (p > 0.05) downregulation of TNF-α in serum samples of animals treated with Miet and piroxicam was observed as compared with control group. Furthermore, Miet significantly halted blood vessels formation in CAM assay. Overall, data of the current study highlight that M. indicus has anti-inflammatory and anti-angiogenic potentials, and, thus, can potentially be used as an adjuvant therapy in solid tumours management.

HPLC Analysis and In Vivo Renoprotective Evaluation of Hydroalcoholic Extract of Cucumis melo Seeds in Gentamicin-Induced Renal Damage.

BACKGROUND AND OBJECTIVES: Cucumis melo, of family Cucurbitaceae, has traditionally been used to treat variety of kidney disorders. However to best of our knowledge there is no scientific study available that validates its renaoprotective uses. Therefore, this study aimed to evaluate nephroprotective effects of hydroalcoholic extract of Cucumis melo seeds (CMHE) and to identify its phytoconstituents. MATERIALS AND METHODS: HPLC was performed to identify key phytochemicals of CMHE. Gentamicin (100 mg/kg/day, i.p) was administered to induce nephrotoxicity in Swiss albino mice for 8 days. Gentamicin (100 mg/kg/day, i.p) and oral CMHE were co-administered to mice at doses of 250 and 500 mg/kg to evaluate protective effects of CMHE. Normal control group mice were administered normal saline. Changes in body weights, biochemical and histopathological studies were conducted to establish nephroprotective effects of CMHE. Results: HPLC analysis indicated presence of quercetin, m-coumaric acid, gallic acid, chlorogenic acid, and trans-4-hydroxy-3-methoxy cinnamic acid in CMHE. Mice treated with CMHE showed significant increase in body weight and decrease in kidney weight as compared with toxic control group. Dose-dependent significant decrease in total blood urea nitrogen, serum creatinine, serum urea, and uric acid levels were observed in CMHE-treated groups as compared with toxic control group. Histopathological analysis of CMHE-treated groups showed improvement in kidney structures as compared with toxic control group. Conclusions: Biochemical, histopathological, and phytochemical screening of hydroalcoholic extract of Cucumis melo seeds suggest that it has nephroprotective potential. Furthermore, standardization of extract against identified phytochemicals, as well as long-term toxicological studies are suggested before commencement of clinical trials.