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In a search of new potentially active antitubercular agents, here we have initiated with pharmacophore development, virtual screening and molecular docking studies to know flexible binding modes with target cavity of DprE1 enzyme. We have designed and synthesized 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives and evaluated for antitubercular activity with specific DprE1 inhibition. The various steps have been completed by performing condensation of 6-(trifluoromethyl)quinazoline-2-carboxylic acid, aromatic aldehydes, methanol, Hydrazine hydrate, -(trifluoromethyl)quinazoline-2-carbohydrazide, 6-(trifluoromethyl)-N′-methylenequinazoline-2-carbohydrazide to obtained 6-(trifluoromethyl)-N-(4-oxothiazolidin-3-yl)quinazoline-2-carboxamide derivatives (3a–r) in better yields. Synthesized derivatives were characterized for their spectral analysis. These compounds have been screened for their in vitro antitubercular activity against Mycobacterium tuberculosis H 37 RV. The compounds 3a (MIC-1.27 μM); 3e (MIC-1.12 μM); 3p (MIC-1.18 μM); and 3r (MIC-0.96 μM); exhibited notable in vitro antitubercular activity compare to the reference standard, Isoniazid. These four compounds were screened for DprE1 enzyme assay. Among those 3e and 3r has shown strong DprE1 inhibition, these compounds were substituted with nitro and hydroxyl group. Image 1 • As per WHO report, tuberculosis (TB) is one of the leading cause of death in infectious disease across the globe. • Molecular modeling approach yielded 18 new quinazoline-2-carboxamide derivatives. • Newly synthesized derivatives studied for In vitro antitubercular activity. • Four compounds have shown better DprE1 Inhibitory Activity. [ABSTRACT FROM AUTHOR]

Bladder cancer is one of the deadly cancers with very limited options of treatment and lack of new drugs. Cisplatin, doxorubicin and thiotepa are the drugs mostly used in therapy. Nine new N-cycloheptyl-substituted- 2,3-dihydro-1,3- benzothiazole-2-carboxamide derivatives were designed using structure based drug discovery. The designed compounds were docked to ascertain their binding against balder cancer cell lines (PDB code 3ERT). structure. The designed compounds were synthesised and characterized using different spectroscopic techniques. These novel compounds were evaluated on the MTT assay for there in vitro efficiency using the TCP1020 cell lines. The compounds 4e and 4i shown good inhibition. Two compounds of the series exhibit promising results which are in agreement with the in silico studies. The most potent compound against TCP1020 cell lines was compound 4i; IC50 = 7.8 μM. The activity of the 4i will be due to the inhibition of estrogenic binding receptor. [ABSTRACT FROM AUTHOR]

The last twenty years have seen noteworthy success in efforts to control HAT (Human African Trypanosomiasis) in Africa. HAT is a neglected tropical disease with major public health and economic effects in sub-Saharan Africa, and its effects on livestock productivity and development are considered major constraints to alleviating poverty in this region. The identification of important chemical features using the existing molecules will be helpful to discover the potent candidate to treat HAT. The development of novel HAT inhibitors is done using pharmacophore based virtual screening and docking study. The 3DQSAR was also performed to determine the predicted biological activity. The best hypothesis from PHASE, gave the five point pharmacophore hypothesis, AAPRR.687 with two hydrogen bond acceptors (A), two aromatic rings (R) and one charged group (P). Amongst them the pharmacophore hypothesis yielded a statistically significant 3D-QSAR model with 0.9521 as coefficient of determination (r2), a Pearson coefficient of 0.8796 and good F value and was considered to be the best pharmacophore hypothesis. The developed pharmacophore based 3D-QSAR model was validated by predicting the activity of test set molecules. The squared predictive correlation coefficient (q2) of 0.7359 was observed between experimental and predicted activity values of test set molecules. The developed pharmacophore was used to screen the chemical database. Subsequently the screened compounds were filtered by molecular docking. Finally five compounds were obtained as novel lead against human African trypanosomiasis. [ABSTRACT FROM AUTHOR]