Conventional and microwave-assisted organic synthesis of novel antimycobacterial agents bearing furan and pyridine hybrids.

Drug resistance in tuberculosis poses a serious threat to humanity because currently available antitubercular drugs are ineffective against Mycobacterium tuberculosis (M. tuberculosis). As a result, the approval of Bedaquiline and Delamanid for the treatment of drug-resistant tuberculosis was accelerated. Still, there is an urgent need to search for new antitubercular drugs with novel mechanisms of action (MoA). Due to this, we have designed a synthetic strategy by utilizing microwave-assisted organic synthesis. We have compared our method with the conventional procedure, and the data show that our procedure is more effective in the preparation of title compounds. A unique series of 1-(2-(furan-2-yl)-5-(pyridin-4-yl)-1,3,4-oxadiazol-3(2H)-yl)-3-(aryl)-prop-2-en-1-ones (5a-o) was synthesized utilizing conventional and microwave-assisted techniques. Synthetic compounds were investigated for antitubercular activity against Mycobacterium TB H37 Ra and Mycobacterium bovis (M. bovis). Compound 5b was reported to be the most effective against M. tuberculosis H37 Ra (97.69 percent inhibition at 30 µg/ml) and M. bovis (97.09 percent inhibition at 30 µg/ml). An in silico binding affinity study of mycobacterial enoyl-acyl carrier protein reductase (InhA) reveals the binding mechanism and thermodynamic interactions that determine these molecule's binding affinity. Compound 5b had a high glide score of -8.991 and low glide energy of -49.893 kcal/mol.

Utility of Breast MRI for Further Evaluation of Equivocal Findings on Digital Breast Tomosynthesis.

OBJECTIVE: The purpose of this study is to evaluate the utility of MRI as a problem-solving tool for equivocal findings on diagnostic digital mammography (DM) and digital breast tomosynthesis (DBT). MATERIALS AND METHODS: Breast MRI examinations performed from March 2011 to November 2014 were retrospectively reviewed to identify those examinations that were performed to further assess equivocal findings on combined DM and DBT (DM/DBT) examinations. All patients underwent diagnostic ultrasound in conjunction with their DM/DBT examination. Imaging reports were retrospectively reviewed for BI-RADS findings and assessments of diagnostic DM/DBT and diagnostic MRI examinations. A review of the electronic medical records provided information on demographic data, cancer diagnoses, and pathologic findings. Differences in the positive predictive values and negative predictive values of DM/DBT and MRI were compared using a generalized estimating equation for correlated binary data. RESULTS: Of 5330 MRI examinations performed during the study, 67 (1%) were performed for evaluation of an equivocal finding, including 27 asymmetries (40%), 16 focal asymmetries (24%), five masses (7%), and 19 architectural distortion (28%). MRI correlates were identified in 22 of 67 examinations (33%). Biopsies yielded a cancer diagnosis for five of 67 patients (7%). For MRI, the positive predictive value and negative predictive value were 19% and 98%, respectively, whereas for DM/DBT they were 6% and 90%, respectively (p = 0.009 and p = 0.059, respectively). The frequency of recommendations for breast MRI to evaluate equivocal findings decreased exponentially in the 3 years after DBT implementation. CONCLUSION: As clinical implementation of DBT becomes increasingly widespread, breast radiologists need an algorithm for addressing the small number of inconclusive findings that remain equivocal despite thorough DM/DBT and ultrasound examinations. Breast MRI is a useful adjunctive tool for these selected cases.