DETERMINATION OF 5H-BENZO[2,3][1,4]OXAZEPINO[5,6-B]INDOLES IN RAT PLASMA BY REVERSED-PHASE HIGH-PERFORMANCE LIQUID CHROMATOGRAPHIC-ULTRAVIOLET METHOD: APPLICATION TO PHARMACOKINETIC STUDIES

Objective: Recently, we reported newly synthesized 5H-benzo[2,3][1,4]oxazepino[5,6-b]indole) derivatives and proved their cytotoxicity against hepatocellular carcinoma specific Hep-G2 cell lines. We attempted herein to describe a reversed-phase high-performance liquid chromatographic method for the determination of three most active compounds 6a, 10a, and 15a in rat plasma to predict their pharmacokinetics parameters before in vivo study.Methods: A rapid and sensitive reversed-phase high-performance liquid chromatographic was employed for the determination of 6a, 10a, and 15a in rat plasma. Each compound was separated by a gradient elution of acetonitrile and water with 1 mL/min flow rate. The detector was set at 270, 285, and 275 nm for 6a, 10a, and 15a and the recorded elution times were 2.00, 2.87, and 1.88 min, respectively.Results: The calibration curve was linear with R2 of 0.938, 0.875, and 0.923 over the concentration range of 0.1–50 μg/mL. The inter- and intra-day variations of the assay were lower than 12.26%; the average recovery of 6a, 10a, and 15a was 97.31, 92.56, and 95.23 % with relative standard deviation of 2.12%, 3.25%, and 2.28%, respectively. The Cmax and Tmax were ~ 46.34, 18.56, and 25.65 μg/mL and 2.0, 4.0, and 4.0 h for 6a, 10a, and 15a, respectively, which indicate a robust method of detection in the present experiment.Conclusion: The study suggests that all of the three compounds have a lower rate of absorption, higher volume of distribution, and lower clearance rate, indicating good therapeutic response for in vivo activity.Â

OXIDATIVE STRESS-BASED HEPATOTOXICITY OF DULOXETINE IN WISTAR RATS

Objective: Duloxetine, a selective serotonin and noradrenaline reuptake inhibitor used in major depressive disorders, urinary incontinence and diabetic peripheral neuropathic pain. It is reported to be associated with several types of liver injuries, including hepatocellular, cholestatic and mixed hepatocellular-cholestatic patterns. The objective of this study was to assess the effect of duloxetine or its metabolites on oxidative stress-induced liver damages.Methods: In this study, animals were divided into five groups. In the first group, the only vehicle was given orally for 21 d. The second group has been considered as hepatotoxic control group where Erythromycin was given orally for 14 d and remaining three groups have been considered as test groups where duloxetine, fluvoxamine and duloxetine along with fluvoxamine were administered orally for 21 d. Liver GSH, oxidised lipid (malonaldehyde MDA), superoxide dismutase (SOD), catalase (CAT), protein carbonyl (PC) and plasma alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) levels were measured to determine the level of hepatotoxicity. Scanning electron microscopy (SEM) study of liver tissues was also performed to examine the liver injuries.Results: GSH and SOD levels were found to be decreased in duloxetine-treated groups with respect to the hepatotoxic control group, whereas increased level of MDA, CAT and PC signify the damages of liver cells. Increased level of plasma ALT, AST and ALP at the same time indicated liver tissue damage. Opposite effects were observed in the case of duloxetine and fluvoxamine-treated groups. SEM of liver tissues revealed that the tissue injury occurred in Duloxetin treated groups, whereas the restoration of normal tissue architecture took place due to the administration of duloxetine and fluvoxamine-treated groups.Conclusion: Our results collectively indicated that hydroxylated and epoxide metabolites of duloxetine might have hepatotoxic potential due to oxidative stress produced by the release of free radicals or reactive oxygen species

A METHOD FOR DETERMINING 1,4-BENZOTHIAZINE DERIVATIVES IN RAT PLASMA BY HPLC AND ITS APPLICATION TO A PHARMACOKINETIC STUDY

Objective: The objective of the study was to develop, optimize and validate of a new reverse-phase high-performance liquid chromatography (RP-HPLC) method for the determining 1,4-benzothiazine derivatives (AR13 and AR15) in a biological sample of rat plasma. The 1,4-benzothiazine derivatives are produced by the synthetic reactions.Methods: RP-HPLC separation was performed using an ODS-2 Hypersil column with gradient elution mobile phase consisting of water-acetonitrile for AR13 and AR15 (1:9 v/v, 3:7 v/v) at room temperature 1 ml/min flow rate, and interfaced with photodiode array detector (PDA) detector, 233 nm, 235 nm respectively.Results: A linear response was obtained between (range from 0.100-10.00 mg/ml) AR13 and (range from 0.096–9.88 mg/ml) AR15 with correlation coefficient 0.999 and 0.998. The linearity range of both AR13 and AR15 was 101.65±1.5 and 98.78±1.7.Conclusion: It was concluded that the method was simple, accurate, sensitive, accurate and reproducible and has been successfully applied to the pharmacokinetic study of AR13 and AR15 in rat plasma

ANTIDIABETIC AND HYPOLIPIDEMIC EFFECT OF FICUS RACEMOSA PETROLEUM ETHER EXTRACT IN STREPTOZOTOCIN INDUCED DIABETIC ALBINO RATS

Objective: The present study was undertaken to evaluate the antidiabetic, hypolipidemic and toxic effects of petroleum ether extract of FR (PEFR) using streptozotocin (STZ) induced diabetic rats. Methods: Diabetes was induced by administration of STZ (50 mg/kg) intraperitonially (i. p.) to albino rats. PEFR was administered once in a day for a period of seven days at doses of 100, 200 and 300 mg/kg according to body weight. Blood glucose and body weight changes were measured at different (1st, 3rd, 5th, and 7th) days of experiment. Serum lipid profile (TC, TG, LDL, VLDL, and HDL) and serum hepatic biomarker enzymes (SGOT and SGPT) levels were measured, and various antioxidant parameters in liver and pancreas were also determined at the end of experiment.Results: Our results collectively suggested that oral administration of PEFR significantly reduced blood glucose level and restored body weight. This extract also reduced serum cholesterol, triglycerides, LDL, VLDL and improved HDL as compared with diabetic control group, signified hypolipidemic action. It increased glutathione and various enzyme levels (catalase and superoxide dismutase) in the pancreas at the same time. Various oxidative stress parameters like thiobarbituric acid reactive substances and protein carbonyl levels in liver were decreased after PEFR administration with respect to diabetic control rats.Conclusion: PEFR possessed antidiabetic, antioxidant and hypolipidemic activities in STZ induced diabetic rats, which supported the use of FR as a food supplement for future drug design perspective.Â

Design and synthesis of 1,4-benzothiazine derivatives with promising effects against colorectal cancer cells

<p>In this study, we designed and synthesized a series of 1,4-benzothiazine and evaluated them for anticancer activity toward HT-29 human colon cancer cells using SRB assay. Before the synthesis, docking studies were performed using various molecular targets of colon cancer including IL-2, IL-6, COX-2, caspase-3, and caspase-8. The molecular dynamic (MD) simulation was also executed to examine the stability of ligand-receptor complex of more stable dock conformation. Further computational study was carried out in order to predict the pharmacokinetic profile of titled compounds. Among 34 tested compounds, compounds <b>AR13</b> and <b>AR15</b> were found to be active against HT-29 cells (GI₅₀ < 10 μM)_. Moreover, Compounds <b>AR5</b>, <b>AR22</b>, and <b>AR34</b> showed the moderate activity with GI₅₀ < 70 μM. The binding energy was found to be > −5 kcal/mol for <b>AR13</b> and <b>AR15</b> with all the molecular targets and the ligand-protein complex was found stable after its formation. Again, computational analysis revealed that both molecules <b>AR13</b> and <b>AR15</b> had good ADMET profiling. These encouraging outcomes allowed us to conclude that both <b>AR13</b> and <b>AR15</b> may emerge as lead compounds against colon cancer.</p

Abstracts of National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020

This book presents the abstracts of the papers presented to the Online National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020 (RDMPMC-2020) held on 26th and 27th August 2020 organized by the Department of Metallurgical and Materials Science in Association with the Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, India. Conference Title: National Conference on Research and Developments in Material Processing, Modelling and Characterization 2020Conference Acronym: RDMPMC-2020Conference Date: 26–27 August 2020Conference Location: Online (Virtual Mode)Conference Organizer: Department of Metallurgical and Materials Engineering, National Institute of Technology JamshedpurCo-organizer: Department of Production and Industrial Engineering, National Institute of Technology Jamshedpur, Jharkhand, IndiaConference Sponsor: TEQIP-