Characterization, molecular modeling and pharmacology of some 2́-hydroxychalcone derivatives as SARS-CoV-2 inhibitor.

This work presented the microwave assisted synthesis of six new 2́-hydroxychalcones and their characterization based on FTIR, UV-Vis, 1H NMR, and mass spectral analysis. Quantum chemical studies confirmed the structures of prepared chalcones. Antioxidant, in vitro antimicrobial and in silico antiviral studies have been performed to evaluate their biological performance. Results of molecular docking of prepared 2́-hydroxychalcones against SARS-CoV-2 (7BQY) main protease disclosed their inhibition which is comparable to standard, remdesivir and better than hydroxychloroquine (HCQ). ADMET prediction revealed them to be non-carcinogenic and relatively safe.

Structural modification of aspirin to design a new potential cyclooxygenase (COX-2) inhibitors.

Aspirin (Asp) is one of the most important and ancient member of nonsteroidal anti-inflammatory drugs (NSAID), commonly used in medication of fever, pain and inflammation. It can inhibit the synthesis of prostaglandin by blocking the cyclooxygenase (COX). Attempts have been taken to analyze aspirin together with some of its modified derivatives applying quantum mechanical calculations in order to compare their physicochemical and biochemical properties. Density functional theory (DFT) with B3LYP/6-31G (d, p) basis set has been employed to elucidate their thermal, molecular orbital, equilibrium geometrical properties in gas phase. Molecular docking and nonbonding interactions have been performed against human cyclooxygenase-2 protein 5F1A to investigate the binding affinity and mode(s) of newly designed aspirin derivatives. ADMET prediction has been utilized to compare the absorption, metabolism, and carcinogenic properties of new derivatives with parent drug (Asp). Thermal and geometrical results support the thermochemical stability and equilibrium geometry of all the structures. From the molecular docking simulation, most of the derivatives exhibited better binding affinity than parent drug (Asp) with the receptor protein (5F1A). ADMET prediction disclosed the improved pharmacokinetic properties with lower acute oral toxicity of some derivatives. Based on quantum chemical, molecular docking and ADMET analysis, this investigation can be useful to understand the physicochemical and biochemical/biological activities of Asp and its modified derivatives to search a new antipyretic analgesic drug.

Optimization of structures, biochemical properties of ketorolac and its degradation products based on computational studies.

BACKGROUND: Ketorolac (KTR) is used as an analgesic drug with an efficacy close to that of the opioid family. It is mainly used for the short term treatment of post-operative pain. It can inhibit the prostaglandin synthesis by blocking cyclooxygenase (COX). METHODS: In this investigation, the inherent stability and biochemical interaction of Ketorolac (KTR) and its degradation products have been studiedon the basis of quantum mechanical approaches. Density functional theory (DFT) with B3LYP/ 6-31G (d) has been employed to optimize the structures. Thermodynamic properties, frontier molecular orbital features, dipole moment, electrostatic potential, equilibrium geometry, vibrational frequencies and atomic partial charges of these optimized structureswere investigated. Molecular docking has been performed against prostaglandin H2 (PGH2) synthase protein 5F19 to search the binding affinity and mode(s). ADMET prediction has performed to evaluate the absorption, metabolism and carcinogenic properties. RESULTS: The equilibrium geometry calculations support the optimized structures. Thermodynamic results disclosed the thermal stability of all structures. From molecular orbital data, all the degradents are chemically more reactive than parent drug (except K3). However, the substitution of carboxymethyl radicalin K4 improved the physicochemical properties and binding affinity. ADMET calculations predict the improved pharmacokinetic and non-carcinogenic properties of all degradents. CONCLUSION: Based on physicochemical, molecular docking, and ADMET calculation, this study can be helpful to understand the biochemical activities of Ketorolac and its degradents and to design a potent analgesic drug.

Non Obstetric Causes and Presentation of Acute Abdomen among the Pregnant Women.

OBJECTIVE: To identify the non-obstetric causes and presentation of acute abdomen among pregnant women. MATERIALS AND METHODS: This was a cross sectional hospital-based study among 128 pregnant women by face to face interview using a semi-structured questionnaire. This study was conducted at the Gynecology & Obstetric Ward of 250 Bed General Hospital, Noakhali, Bangladesh, from January to August 2013. Data were analyzed by a software package used for statistical analysis (SPSS) version 11.5 (SPSS, Inc., Chicago, IL, USA). RESULTS: Mean age of participants was 25±4 years. Our findings showed that 81% were Muslim, 67% were lower middle income group, as well as 47% completed primary level of education. The results revealed that 28% had biliary ascariasis, 24% had peptic ulcer disease and 10% had lower urinary tract infection. We also found that 6% had acute pyelonephritis, 6% had acute gastroenteritis, 6% had acute cholecystitis, 6% had acute appendicitis, 2% had acute pancreatitis, 3% had choledocolithiasis, 2% had ovarian solid mass, 2% had twisted ovarian cyst, 4% had renal colic, and 1% had renal calculus. In non-obstetrical presentation of acute abdomen, the study found that 84% of respondents complained their pain lasting more than 24 hours. Besides, half of respondents felt pain in epigastrium and right hypochondrium. Cramping, prickling and aching type of pain were more, while 66% suffered from continuous pain. Our results also showed that 73% did not explain any aggravating factor and relieving factor, and the rest said food, fasting state and position change aggravated pain as well as relieved pain. CONCLUSION: The study concludes that precise diagnosis of the acute abdomen in pregnant women by continual updating of abdominal assessment knowledge, and clinical skills is necessary in the management of abdominal pain in obstetric settings.