SIMULTANEOUS ESTIMATION OF AZILSARTAN AND CILNIDIPINE IN BULK BY RP-HPLC AND ASSESSMENT OF ITS APPLICABILITY IN MARKETED TABLET DOSAGE FORM

Objective: This study aims to build up the RP-HPLC process for Azilsartan and Cilnidipine and authenticate the RP-HPLC process according to ICH validation code Q2R1. Methods: System suitability testing was performed to discover the qualifying criterion of the method by injecting the identical standard solution of Azilsartan 40μg/ml and Cilnidipine 10μg/ml in mixture/combination in subsequent optimized chromatographic conditions and the chromatogram was recorded. Moreover, the planned method was validated as per ICH guideline Q2R1 for the following parameters: linearity and range, precision, accuracy, robustness, and determined % recovery. Results: The outcomes of %RSD for retention time and peak area were found to be 0.65 and 1.32 for Azilsartan and 0.85 and 1.90 for Cilnidipine. The correlation coefficient, y-intercept, slope of the regression line were 0.9996,-1127.1, 3313.9, and 0.9993, 1460.2, 2876.4 for Azilsartan and Cilnidipine, respectively. Moreover, the range of this method was observed to be 40-240μg/ml and 10-60 μg/ml for Azilsartan and Cilnidipine, standard concentrations respectively. The % RSD achieved for precision (repeatability) was observed in the range of 1.57 to 2.43 for Azilsartan and 0.70 to 1.88 for Cilnidipine. The % accuracy was found in the range of 96.96 to 101.92% w/w for Azilsartan and 99.19 to101.96%w/w for Cilnidipine. The percent recovery values achieved for Azilsartan were in the range of 99.87 to 106.39% w/w and for Cilnidipine in the range of 94.51 to 105.96% w/w. Conclusion: The author concludes that the simultaneous estimation of Azilsartan and Cilnidipine with predefined objectives was successfully achieved. Moreover, the method was found to be steadfast for the quantification of Azilsartan and Cilnidipine in marketed tablet dosage forms

Effect of remdesivir on mortality rate, need of intubation and mechanical ventilation in COVID-19 positive patients: a retrospective observational study

Background: The symptoms of SARS-CoV-2 infection vary widely, from asymptomatic disease to pneumonia and life-threatening complications, including acute respiratory distress syndrome, multisystem organ failure, and ultimately, death. Remdesivir has broad spectrum of activity against members of several virus families, including filoviruses and coronaviruses. Remdesivir is a potent inhibitor of SARS-CoV-2 replication in human nasal and bronchial cells. Methods: This is a prospective and observational study conducted in patients of either gender, age more than 18 years with confirmed diagnosis of COVID-19 by RT-PCR. A predesigned, pretested and semi structured questionnaire containing socio demographic details like age, sex, BMI, comorbidities, findings of systemic examination of the cases, dose and duration of Remdesivir received and adverse effect due to therapy was used to collect the data. Results: Mean age of the patients were 56.19±10.93 years. Male patients were 66% and 34% patients were female. After receiving the remdesivir, 43% of the patients needed bag mask and 27% of the patients maintained on room air oxygen. Non-invasive ventilation required in 19% of the patients and 11% of the patient required mechanical ventilation. s14% of the patients needed admission in the ICU. 3.5% of the patients were died and 96.5% patients were discharged from the hospital. Conclusions: Remdesivir reduces the need of non-invasive oxygenation and mechanical ventilation. Mortality was seen in 3.5% patients, henceforth remdesivir, is an effective drug for moderate to severe COVID-19, if given in early stages of infection

Ultrasound-promoted One-Pot, Three Component Synthesis Of Novel 5-Amino-2-(4-Chlorophenyl)-7- Substituted Phenyl-8,8a-Dihydro-7H-[1,3,4]Thiadiazolo[3,2-A]Pyrimidine-6-Carbonitrile Derivatives

The 19th International Electronic Conference on Synthetic Organic Chemistry session General Organic SynthesisHere is the report of an environment friendly, rapid, and convenient one-pot ultrasound-promoted synthesis of 5-amino-2-(4-chlorophenyl)-7- substituted phenyl-8,8a-dihydro-7H-[1,3,4]thiadiazolo[3,2-a]pyrimidine-6-carbonitrile derivatives. Multi-component reactions are useful for the creation of chemical libraries of drug-like compounds with levels of molecular complexity and diversity. 1,3,4-Thiadiazolo[3,2-a]pyrimidine skeleton belongs to a well-known and important class of fused heterocycles prevalent in a number of natural products of biological activities including antitumor, fungicidal, antibacterial, and herbicidal, hence, prompted us to synthesis 1,3,4-Thiadiazolo[3,2-a]pyrimidines. The final ten derivatives were obtained in excellent yield through a one-pot, three component condensation reaction of aldehyde, 4-chlorophenyl-2-aminothiadiazole, and malononitrile in 10-12 ml of ethanol as solvent and sodium hydroxide as a catalyst. (VCX 500-220, Ultrasound Solid probe, irradiation at 800C and 20% amplitude). We have carried out the same reaction by conventional method, which requires 9-10 hrs of refluxing and yield is lesser. Because of the advantage of faster reaction rates and better yields, use of Ultrasound solid probe, was found to be more suitable for this reaction. Structure of the synthesized derivatives was confirmed by IR, NMR and Mass spectral stud

Structure-Based Site of Metabolism (SOM) Prediction of Ligand for CYP3A4 Enzyme: Comparison of Glide XP and Induced Fit Docking (IFD)

Metabolism is one of the prime reasons where most of drugs fail to accomplish their clinical trials. The enzyme CYP3A4, which belongs to the superfamily of cytochrome P450 enzymes (CYP), helps in the metabolism of a large number of drugs in the body. The enzyme CYP3A4 catalyzes oxidative chemical processes and shows a very broad range of ligand specificity. The understanding of the compound’s structure where oxidation would take place is crucial for the successful modification of molecules to avoid unwanted metabolism and to increase its bioavailability. For this reason, it is required to know the site of metabolism (SOM) of the compounds, where compounds undergo enzymatic oxidation. It can be identified by predicting the accessibility of the substrate’s atom toward oxygenated Fe atom of heme in a CYP protein. The CYP3A4 enzyme is highly flexible and can take significantly different conformations depending on the ligand with which it is being bound. To predict the accessibility of substrate atoms to the heme iron, conventional protein-rigid docking methods failed due to the high flexibility of the CYP3A4 protein. Herein, we demonstrated and compared the ability of the Glide extra precision (XP) and Induced Fit docking (IFD) tool of Schrodinger software suite to reproduce the binding mode of co-crystallized ligands into six X-ray crystallographic structures. We extend our studies toward the prediction of SOM for compounds whose experimental SOM is reported but the ligand-enzyme complex crystal structure is not available in the Protein Data Bank (PDB). The quality and accuracy of Glide XP and IFD was determined by calculating RMSD of docked ligands over the corresponding co-crystallized bound ligand and by measuring the distance between the SOM of the ligand and Fe atom of heme. It was observed that IFD reproduces the exact binding mode of available co-crystallized structures and correctly predicted the SOM of experimentally reported compounds. Our approach using IFD with multiple conformer structures of CYP3A4 will be one of the effective methods for SOM predictionAuthor A.P.S. is grateful to the University Grants Commission, New Delhi for the financial assistance under the major research project (42-677/2013 (SR)) and Dr. Babasaheb Ambedkar Marathwada University, Aurangabad for the research grant (STAT/VI/RG/Dept/2019-20/309-10)S

Triethyl ammonium sulphate catalyst one pot, Solvent free synthesis of novel Coumarin derivatives as antimicrobial agents

The 20th International Electronic Conference on Synthetic Organic Chemistry session Ionic LiquidsThe work reports synthesis of 15 novel 3-((dicyclohexylamino)(substituted phenyl/heteryl)methyl)-4-hydroxy-2H-chromen-2-one derivatives 4 (a-o) as potential antimicrobial agents in solvent-free condition using Triethyl ammonium sulphate [Et3NH][HSO4] as an efficient, eco-friendly and reusable catalyst. Compared to other methods, this new method consistently has advantages, including excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. The heterocyclic compound Coumarin, is associated with diverse biological activities of immense importance. Due to the presence of coumarin moiety in various pharmaceutically active compounds, we planned the green synthesis of a series of 15 novel compounds containing coumarin moiety coupled with dicyclohexyl rings by an eco-friendly ionic-liquid mediated protocol at room temperature by stirring. The structures of the synthesized compounds were confirmed by spectral characterization such as IR, 1H NMR, 13CNMR and Mass spectral studies. All the synthesized compounds 4 (a-o) were evaluated for anti-fungal and antibacterial activities and have exhibited promising antimicrobial activit

Synthesis and biological evaluation of new quinazolinone derivatives

New N-substituted-2-methyl quinazolin-4(3H)-ones derivatives comprising 1,3,4-thiadiazole, Schiff bases and 2-azetidinone moieties are reported. The structures of the newly prepared compounds were confirmed by FT-IR and 1H NMR spectra. The compounds were also evaluated for their antimicrobial, antioxidant and study of inhibition on some enzymes activities. The results suggest that the compounds possess broad spectrum of in-vitro antimicrobial activity. Antioxidant results obtained into the present study indicate that compound 5 show moderate better scavenging activity. Compound 5 demonstrated inhibitory effects on GOT, GPT, GGT and ALP activities, and these effects increase with increasing the concentration of the compound

Ionic liquid [Et3NH][HSO4]catalyslyzed multicomponent synthesis of 6 amino-4-(Substituted phenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile

The 20th International Electronic Conference on Synthetic Organic Chemistry session Ionic LiquidsA series of 6-amino-4-substituted-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitriles 5(a-j) as a potent anticancer agent were synthesized via one-pot, four-component condensation reaction of aryl aldehydes, ethyl acetoacetate, malononitrile, and hydrazine hydrate in solvent-free conditions using ionic liquid [Et3NH][HSO4] as an efficient, eco-friendly and reusable catalyst. The Multi component coupling reactions (MCRs) indicate a highly appreciated synthetic tool for the establishment of novel and complex molecular scaffold with a minimum number of synthetic steps with the advantage like shorter reaction times, lower costs, high degrees of atom economy etc. From the literature survey it is found that dihydropyrano[2,3-c]pyrazole derivatives posses very important biological activities, including anticancer, antiinflammatory, antimicrobial, inhibitors of human Chk1 kinase, molluscicidal, and insecticidal activities. The solvent used in conventional organic synthesis are suffered by many disadvantage like environmental hazards, toxicity, volatile nature, expensive etc. A new term ‘designer solvents’ referring to Ionic liquids because of their adjustable physical and chemical properties with the change in selected cationic and anionic combination. Ionic liquids have become a promising alternative media for various chemical processes due to their properties including good solvating capability, negligible vapour pressure, non-inflammability, ease of recyclability, controlled miscibility and high thermal stability. Herein we are reporting the use of acidic Bronsted ionic liquid(ABILs) [Et3NH][HSO4] triethyl ammonium sulphate for the synthesis of biologically important scaffold 6-amino-4-(substituted phenyl)-3-methyl-2,4-dihydropyrano[2,3-c]pyrazole-5-carbonitrile . Compared to other methods, this new method has advantages, such as excellent yields, a short reaction time, mild reaction conditions and catalyst reusability. The synthesized derivatives 5(a-j) were characterized by FTIR, 1HNMR, 13CNMR and mass spectral dat

Molecular sieves and Ultrasound assisted Synthesis of Novel 1,3,4-oxadiazole-2-thiones derivatives as potential antifungal Agents

The 19th International Electronic Conference on Synthetic Organic Chemistry session Bioorganic, Medicinal and Natural Products ChemistryIn the category of microorganism, fungi are considered as the special class of microbes responsible for opportunistic pathogenic infections in humans species. Due to the side effects of commercially available antifungal drugs and the emergence of new drug resistant fungal species in the past few years has forced the researchers to search for novel and efficient antifungal drug molecules. The 1,3,4-oxadiazoles scaffold is associated with diverse biological activities. The multipurpose use of the Mannich bases in pharmaceutical chemistry provoked us to prepare a new series of 1,3,4-oxadiazole Mannich bases derivatives, as antifungal agents. Herein we report Molecular sieves and Ultrasound assisted synthesis of novel series of Mannich bases of the 5-substituted 1,3,4-oxadiazole-2-thiones by amino methylation with paraformaldehyde and substituted primary / secondary amines and their evaluation for antifungal activity .The structures of the newly synthesized compounds were determined by IR, NMR and Mass spectral study. The synthesized compounds exhibited interesting moderate to excellent antifungal activity against Candida albicans (NCIM 3557),Candida albicans(NCIM3471), Candida glabrata(NCIM3237), Cryptococcus neoformans (NCIM 3542),Cryptococcus neoformans(NCIM 3378),Aspergillus fumigates(NCIM 902), Aspergillus niger( NCIM 628) using Flucanazole as a standard reference drug. The synthesised compounds 6d, 6f ,6g, 6h and 6j exhibited promising antifungal activity as fungi static agent