Antimicrobial and anticancer evaluation of a novel synthetic tetracyclic system obtained by Dimroth rearrangement

A series of pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[4,3-c]pyrimidines were prepared via oxidative cyclization of 4-(2-arylidenehydrazinyl)pyrido [3',2':4,5]thieno[3,2-d] pyrimidines. Dimroth rearrangement of such a series yielded pyrido[3',2':4,5]thieno[2,3-e][1,2,4]triazolo[1,5-c]pyrimidines. The reaction mechanism was proposed and the products were screened for their antimicrobial and anticancer activities. From the antimicrobial screening results, it can be seen that compounds 8c, 9f and 10c showed excellent activity against gram positive bacteria while compounds 10d and 8c showed the highest activity against gram negative bacteria. The results of the anticancer activities showed that compound 9c was the most active against HepG-2 and MCF-7 with IC50 values of 1.19 and 3.46, respectively

Transmission of substituent effects via 1,2,4-triazole ring residue

1012-1016The ionization constants of a series of 5-phenyl-3-substituted phenyl-1,2,4-triazole- 3-carboxylic acids (2a-j), prepared by the base catalysed rearrangement of 2-phenyl-4-arylazo-5-oxazolones (1a-j), and the rate of alkaline hydrolysis of the corresponding methyl esters (3a-j) have been measured in 80% (v/v) ethanol at 30°C and ionic strength of 0.1. Both the equilibrium and rate constants have been correlated by Hammett equation, the values of the reaction constant p being 0.45 and 0.24 respectively. A comparison of presently reported values with those reported in literature for ionization of benzoic acids and alkaline hydrolysis of methyl benzoates indicates that the 1,3-(1,3,4-triazole) ring residue is 39% and 10% efficient in transmitting substituent electronic effects in 2 and 3 respectively

An Efficient Synthesis of Novel Pyrazole-Based Heterocycles as Potential Antitumor Agents

A new series of pyrazolylpyridines was prepared by reaction of ethyl-3-acetyl-1,5-diphenyl-1H-pyrazole-4-carboxylate with the appropriate aldehyde, malononitrile, or ethyl acetoacetate and an excess of ammonium acetate under reflux in acetic acid. Similarly, two novel bipyridine derivatives were prepared by the above reaction using terephthaldehyde in lieu of benzaldehyde derivatives. In addition, a series of 1,2,4-triazolo[4,3-a]pyrimidines was synthesized by a reaction of 6-(pyrazol-3-yl)pyrimidine-2-thione with a number of hydrazonoyl chlorides in dioxane and in the presence of triethylamine. The structure of the produced compounds was established by elemental analyses and spectral methods, and the mechanisms of their formation was discussed. Furthermore, the pyrazolyl-pyridine derivatives were tested as anticancer agents and the results obtained showed that some of them revealed high activity against human hepatocellular carcinoma (HEPG2) cell lines

SARS-CoV-2 vaccination modelling for safe surgery to save lives: data from an international prospective cohort study

Background: Preoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling. Methods: The primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty. Results: NNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year. Conclusion: As global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population