Silver-Catalyzed Asymmetric Double Desymmetrization via Vinylogous Michael Addition of Prochiral α,α-Dicyanoalkenes to Cyclopentendiones.

An asymmetric double desymmetrization methodology has been developed for synthesizing densely functionalized chiral cyclopentylcyclohexane scaffolds. We have constructed four chiral centers, including an all-carbon quaternary stereocenter in a single C-C bond formation event. The methodology has high functional-group tolerance and delivers a broad range of enantioenriched products. This vinylogous Michael addition reaction of prochiral α,α-dicyanocyclohexane to 2,2-disubstituted cyclopentene-1,3-dione is catalyzed by a chiral Ag-(R)-DTBM-SEGPHOS catalyst.

Kinetic Resolution of Electron-Deficient Bromohydrins via Copper(II)-Catalyzed C-C Bond Cleavage.

Herein, we report a nonenzymatic kinetic resolution (KR) of α,ß-unsaturated ketone-derived bromohydrins (up to s = 211) with N-bromosuccinimide (NBS) in the presence of a chiral Cu(II)-Box catalyst via the C-C bond cleavage of the fast reacting enantiomer. A one-pot synthesis-KR approach of the same has also been realized with excellent enantioselectivities (up to 99% ee). Both protocols are found to be effective for a variety of substrates, leading to enantioenriched bromohydrins. The synthetic utility of this process has been demonstrated by exploring a new strategy to convert the resolved enantiomer to an optically active epoxide.

Epidemiological and Time Series Analysis of Tuberculosis with Prediction during COVID-19 Pandemic using ARIMA Model: A Study from Churu District of Rajasthan.

As Tuberculosis (TB) is a major public health problem in India and to achieve the goal of TB elimination, it is important to assess the trend of TB cases and the impact of lockdowns and other restrictions imposed for control of COVID-19 in India on the National TB Elimination Programme. Hence, the present study aims to study the temporal trend of TB cases and assess the impact of lockdown on TB detection. A retrospective record-based study was conducted in a tertiary care institute of India. A time series analysis of TB cases from April 2018 to May 2020 was carried out. An Auto-Regressive Integrated Moving Averages (ARIMA) model was used to forecast TB cases during the lockdown period and the result was compared with actual cases detected. The statistical analysis was accomplished with R software. The time series analysis showed that the projected TB cases in April and May 2020 were 67 and 86, respectively, while the observed cases in these months were 35 and 76. The trend of TB cases during the study period showed no steady increase or decrease and the detection of TB has declined during the COVID-19 lockdown period. The TB cases peaked from April to June and males constitute the majority of TB cases.

Synthesis, DFT Analyses, Antiproliferative Activity, and Molecular Docking Studies of Curcumin Analogues.

With 19.3 million new cases and almost 10 million deaths in 2020, cancer has become a leading cause of death today. Curcumin and its analogues were found to have promising anticancer activity. Inspired by curcumin's promising anticancer activity, we prepared three semi-synthetic analogues by chemically modifying the diketone function of curcumin to its pyrazole counterpart. The curcumin analogues (3a−c) were synthesized by two different methods, followed by their DFT analyses to study the HOMO/LUMO configuration to access the stability of compounds (∆E = 3.55 to 3.35 eV). The curcumin analogues (3a−c) were tested for antiproliferative activity against a total of five dozen cancer cell lines in a single (10 µM) and five dose (0.001 to 100 µM) assays. 3,5-Bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(phenoxy)ethanone (3b) and 3,5-bis(4-hydroxy-3-methoxystyryl)-1H-pyrazole-1-yl-(2,4-dichlorophenoxy)ethanone (3c) demonstrated the most promising antiproliferative activity against the cancer cell lines with growth inhibitions of 92.41% and 87.28%, respectively, in a high single dose of 10 µM and exhibited good antiproliferative activity (%GIs > 68%) against 54 out of 56 cancer cell lines and 54 out of 60 cell lines, respectively. The compound 3b and 3c demonstrated the most potent antiproliferative activity in a 5-dose assay with GI50 values ranging between 0.281 and 5.59 µM and 0.39 and 0.196 and 3.07 µM, respectively. The compound 3b demonstrated moderate selectivity against a leukemia panel with a selectivity ratio of 4.59. The HOMO-LUMO energy-gap (∆E) of the compounds in the order of 3a > 3b > 3c, was found to be in harmony with the anticancer activity in the order of 3c ≥ 3b > 3a. Following that, all of the curcumin analogues were molecular docked against EGFR, one of the most appealing targets for antiproliferative activity. In a molecular docking simulation, the ligand 3b exhibited three different types of interactions: H-bond, π-π-stacking and π-cationic. The ligand 3b displayed three H-bonds with the residues Met793 (with methoxy group), Lys875 (with phenolic group) and Asp855 (with methoxy group). The π-π-stacking interaction was observed between the phenyl (of phenoxy) and the residue Phe997, while π-cationic interaction was displayed between the phenyl (of curcumin) and the residue Arg841. Similarly, the ligand 3c displayed five H-bonds with the residue Met793 (with methoxy and phenolic groups), Lys845 (methoxy group), Cys797 (phenoxy oxygen), and Asp855 (phenolic group), as well as a halogen bond with residue Cys797 (chloro group). Furthermore, all the compound 3a−c demonstrated significant binding affinity (−6.003 to −7.957 kcal/mol) against the active site of EGFR. The curcumin analogues described in the current work might offer beneficial therapeutic intervention for the treatment and prevention of cancer. Future anticancer drug discovery programs can be expedited by further modifying these analogues to create new compounds with powerful anticancer potentials.

Increasing postpartum IUCD coverage through a QI initiative: a step towards reducing the unmet need of postpartum contraception.

BACKGROUND: Unintended pregnancies have a negative impact on the health and economy of a nation, which can be prevented by effective family planning (FP) services. Postpartum intrauterine device (PPIUCD) is a safe and effective FP method which allows women to obtain long-acting contraception before discharge from the point of delivery. We observed poor coverage of deliveries with PPIUCD at our facility. This was the trigger to initiate a quality improvement (QI) initiative to increase the PPIUCD coverage from current rate of 4.5%-10% in 3-month period. METHOD: A fishbone analysis of the problem was done and the following causes were identified: lack of focused counselling for FP, lack of sensitisation and training of resident doctors and inconsistent supply of intrauterine contraceptive devices (IUCDs). A QI team was constituted with representatives from faculty members, residents, interns, nursing officers and FP counsellors. The point of care quality improvement methodology was used. INTERVENTIONS: Daily counselling of antenatal women was started by the counsellors and interns in antenatal wards. A WhatsApp group of residents was made initially to sensitise them; and later for parking of problems and trouble shooting. The residents were provided hands-on training at skills lab. Uninterrupted supply of IUCDs was ensured by provision of buffer stock of IUCDs with respective store keepers. RESULT: The PPIUCD insertion rates improved from 4.5% to 19.2% at 3 months and have been sustained to a current 30%-35% after 1 ½ years of initiation of the project tiding through the turbulence during the COVID-19 pandemic using QI techniques. CONCLUSION: Sensitisation and training of residents as well as creation of awareness among antenatal women through targeted counselling helped improve PPIUCD coverage at the facility. QI initiatives have the potential to facilitate effective implementation of the FP programmes by strategic utilisation of the resources.