Comparative assessment of some benzodiazepine drugs based on Density Functional Theory, molecular docking, and ADMET studies

Benzodiazepines are widely used to treat anxiety, insomnia, agitation, seizures, and muscle spasms. It works through the GABAA receptors to promote sleep by inhibiting brainstem monoaminergic arousal pathways. It is safe and effective for short-term use, and arises some crucial side effects based on dose and physical condition. In this investigation, physicochemical properties, molecular docking, and ADMET properties have been studied. Density functional theory with B3LYP/6-311G+(d,p) level of theory was set for geometry optimization and elucidate their thermodynamic, orbital, dipole moment, and electrostatic potential properties. Molecular docking and interaction calculations have performed against human GABAA receptor protein (PDB ID: 4COF) to search the binding affinity and effective interactions of drugs with the receptor protein. ADMET prediction has performed to investigate their absorption, metabolism, and toxic properties. Thermochemical data suggest the thermal stability; the docking result predicts effecting bindings and ADMET calculation disclose non-carcinogenic and relatively harmless phenomena for oral administration of all drugs

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).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

Selective modification of diclofenac to reduce the adverse effects; A computer-aided drug design approach

Diclofenac (DCF) is a non-steroidal anti-inflammatory drug (NSAID), commonly used for the treatment of pain. It can inhibit prostaglandin synthesis by blocking cyclooxygenase (COX). It shows some crucial side effects like gastrointestinal, cardiovascular, renal, and liver injury. The gastrointestinal injury occurred due to the presence of a carboxylic (COOH) group at the core of DCF. The hydroxyl (OH) portion of COOH was replaced by inserting some new functional groups (CH3, OCH3, CH2NH2, NH2, NHCOCH3, NHCONH2, Cl, CF3) considering the retrosynthetic strategy which reduces gastrointestinal side effects with improved chemical and biological activity. Herein, we have investigated the physicochemical, spectral, molecular dynamics, biological and pharmacokinetic properties of the mentioned analogues. Density functional theory (DFT) and time-dependent DFT along with the B3LYP/6-31g (d,p) basis set have been utilized to calculate their geometrical, chemical, and spectral properties. Molecular docking and non-bonding interactions have been performed against human prostaglandin synthase protein (PDB ID: 5F1A) to investigate their binding affinities, modes, and stability. ADMET and PASS prediction studies were performed to investigate their microbial inhibition and toxicological profile. Quantum chemical calculations and spectral characterization support the geometry of newly designed analogues. From the molecular docking simulation, most of the analogues exhibited better binding affinity than the parent drug except for DCF-2. ADMET calculations predict the improved pharmacokinetic and non-carcinogenic properties of all DCF analogues. Biological activities and drug-likeness indicate that all the analogues of DCF have been exposed to comparatively lower action of the gastrointestinal hemorrhage than DCF and exhibit antipyretic, analgesic, and anti-inflammatory actions as well as performed to overcome the poor absorption or permeation of drugs. Finally, based on the above investigation, this study can be helpful to design a potential drug candidate with improved medicinal action and reduced selective adverse effects

Spectrochemical, biological, and toxicological studies of DDT, DDD, and DDE: An in-silico approach

Pesticides are used to control the various pests and disease carriers. Degradation and/or biotransformation alter their chemical and toxicological nature. An attempt has been taken to investigate the physicochemical, spectral, and toxicological nature of DDT [1, 1'-(2, 2, 2-trichloroethylidene) bis(4-chlorobenzene)] and its major derivatives. DDT is transformed into DDD [l, l-dichloro-2, 2-bis(p,p-chlorophenylethane)], and DDE [l, l-dichloro-2, 2-bis(p,p-chlorophenylethylene)] under reductive dechlorination conditions. They last longer in the fatty tissue due to fat-soluble features, and exhibit some harmful effects on the environment and biological systems. Herein, density functional theory along with the CAM-B3LYP/6-311g ++ (d, p) basis set has been employed to investigate their physicochemical, and spectral properties. In-silico methods were incorporated to evaluate their biological, and toxicological properties. Molecular docking and nonbonding interaction calculations were performed to investigate their binding properties and mode(s) of action against the human estrogen receptor (PDB ID: 6PYF), and serine/threonine-protein kinase PIM-2 (PDB ID: 2IWI). Further, molecular dynamics simulation was performed to check the deformability and interactions of protein and amino acid residues, respectively. ADMET (absorption, distribution, metabolism, excretion, and toxicity) and PASS (prediction of activity spectra for substances) predictions were performed to compare their biological and toxicological properties. DDT has the highest free energy, dipole moment, and chemical reactivity; meanwhile, DDE and DDD have the highest binding affinity against both proteins. All the compounds exhibit hepato-toxicological, neuro-toxicological, and carcinogenic properties which depict their toxicological level. Based on their studied parameters, this study can help to increase awareness and provide a deeper understanding of the biochemical, and toxicological impacts on the environment and biological system