6-Amino-4-aryl-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamides: Synthesis, Biological Activity, Quantum Chemical Studies and In Silico Docking Studies.

New [1,2]dithiolo[3,4-b]pyridine-5-carboxamides were synthesized through the reaction of dithiomalondianilide (N,N'-diphenyldithiomalondiamide) with 3-aryl-2-cyanoacrylamides or via a three-component reaction involving aromatic aldehydes, cyanoacetamide and dithiomalondianilide in the presence of morpholine. The structure of 6-amino-4-(2,4-dichloro- phenyl)-7-phenyl-3-(phenylimino)-4,7-dihydro-3H-[1,2]dithiolo[3,4-b]pyridine-5-carboxamide was confirmed using X-ray crystallography. To understand the reaction mechanism in detail, density functional theory (DFT) calculations were performed with a Grimme B97-3c composite computational scheme. The results revealed that the rate-limiting step is a cyclization process leading to the closure of the 1,4-dihydropyridine ring, with an activation barrier of 28.8 kcal/mol. Some of the dithiolo[3,4-b]pyridines exhibited moderate herbicide safening effects against 2,4-D. Additionally, ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) parameters were calculated and molecular docking studies were performed to identify potential protein targets.

Productivity losses associated with premature mortality due to cancer in Russia: A population-wide study covering 2001-2030.

Aims: Productivity losses related to premature cancer mortality have been assessed for most developed countries but results for Russia are limited to cross-sectional reports. The aim of this study was to quantify productivity costs due to cancer mortality in Russia between 2001 and 2015 and project this to 2030. Methods: Cancer mortality data (2001-2015) were acquired from the State Cancer Registry, whereas population data, labour force participation rates and annual earnings were retrieved from the Federal State Statistics Service. Cancer mortality was projected to 2030 and the human capital approach was applied to estimate productivity losses. Results: The total annual losses increased from US6.5b in 2001-2005 to US$8.1b in 2011-2015, corresponding to 0.24% of the annual gross domestic product. The value is expected to remain high in 2030 (US$7.5b, 0.14% of gross domestic product). Productivity losses per cancer death are predicted to grow faster in women (from US$18,622 to US$22,386) than in men (from US$25,064 to US$28,459). Total losses were found to be highest for breast cancer in women (US$0.6b, 20% of overall losses in women) and lung cancer in men (US$1.2b, 24%). The absolute predicted change of annual losses between 2011-2015 and 2026-2030 was greatest for cervix uteri (+US$214m) in women and for lip, oral and pharyngeal cancers in men (+US$182m). Conclusions: In Russia, productivity losses due to premature cancer mortality are substantial. Given the expected importance especially for potentially preventable cancers, steps to implement effective evidence-based national cancer control policies are urgently required.

2-Amino-4,5-dihydrothiophene-3-carbonitriles: A New Synthesis, Quantum Chemical Studies, and Mannich-Type Reactions Leading to New Hexahydrothieno[2,3-d]pyrimidines.

trans-2-Amino-4-aryl-5-benzoyl-4,5-dihydrothiophene-3-carbonitriles were prepared either by the reaction of 3-aryl-2-cyanothioacrylamides with α-thiocyanatoacetophenone or by the Michael-type addition of cyanothioacetamide to α-bromochalcones followed by intramolecular cyclization. The mechanism of the first reaction was studied using high-level quantum chemical calculations. Density functional theory (DFT) studies were carried out to determine the mechanism of the first reaction. A new approach toward the construction of the thieno[2,3-d]pyrimidine core system was demonstrated by the reaction of the prepared dihydrothiophenes with HCHO and RNH2 under noncatalyzed Mannich conditions.

Breast and cervical cancer incidence and mortality trends in Russia 1980-2013.

BACKGROUND: Breast and cervical cancer are among the leading causes of preventable cancer deaths in women in Russia. The aim of this study is to analyze changes in breast and cervical cancer incidence and mortality trends using data from the Russian State Cancer Registry. METHODS: The age-standardized rates of cervical cancer incidence (1993-2013) and mortality (1980-2013) were analyzed using piecewise linear regression. Age-period-cohort models were used to estimate the temporal effects and provide future predictions. RESULTS: Breast and cervical cancer incidence rates uniformly increased over two decades from 33.0 to 47.0 per 100,000 and from 10.6 to 14.2 per 100,000, respectively. Breast cancer mortality rates however declined from 17.6 to 15.7 in 2013, while cervical cancer mortality increased steadily from 5.6 to 6.7. Breakpoints in the risk occurred in cohorts born 1937-1953, indicating a recent generational decrease in breast cancer mortality, but a concomitant increase in cervical cancer. Cervical cancer has already surpassed breast cancer in terms of years of life lost (YLL) (23.4 per death vs 18.5 in 2009-2013), while future projections suggest that the annual YLL could reach 1.2 million for cervical cancer and (decline to) 1.8 million for breast cancer by the year 2030. CONCLUSION: The temporal patterns of breast cancer incidence and mortality in Russia are in line with other countries in Europe, although cervical cancer rates and the risk of occurrence in recent generations is rapidly increasing; these trends underscore the need to place immediate priority in national cervical vaccination and screening programs.