The concerning rise in emergence and prevalence of resistant strains to drugs of M. tuberculosis has ,the prompted researchers to look for new and effective treatments. With this motive, biscoumarins were identified as the lead molecules on a whole-cell-based screening of several less explored low molecular weight bioactive compounds against M. tuberculosis strains. Among the screened biscoumarins, the highest dock score derivatives were synthesized (a-h) using a programmable microwave synthesizer for better yields and reaction control. The synthesized derivatives were evaluated against H37Rv, H37Ra, M. smegmatis, an MDR surrogate model, and other bacterial strains for the structure-activity response. Assessment of the synthesized library against mycobacterial strains led to the identification of compounds (f and d) as lead anti-tuberculosis agents. Compounds (f and d) exhibited less toxicity against human cell lines. At the same time, it displayed enjoyable activity wherein MIC concentrations were observed to be 16- and 32 µg/mL against the susceptible H37Rv, and H37Ra strains of M. tuberculosis and MIC value of 128 µg/mL for M. smegmatis, respectively. For mechanistic insights and identification of drug binding targets, molecular docking and dynamic simulations were employed for a panel of 16 mycobacterial enzymes essential for mycobacterial growth and survival. These in silico studies revealed the DprE1 enzyme as a druggable target for the anti-tuberculosis activity of the selected biscoumarins derivatives. Further investigation is underway in our laboratory, leading to its development as an anti-tuberculosis drug (animal model studies).

Background: B-cell lymphoma/leukemia gene-2 (Bcl-2) is the first proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 overexpression has been linked to an increase in invasion and migration. Many treatment regimens that target BCL2 have been established and approved, and thus increasing the survival rates of the patients. Aim: The primary goal of this research was to identify new therapeutic compounds that target BCL2 and assess BCL2 expression pattern in BC patients. Methods: We used various bioinformatic tools as well as several in vitro assays to find out the expression and inhibition of Bcl2 in BC. Results: Our study shows that BCL2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets BCL2. Conclusion: Overall, this work shows that BCL2 overexpression accelerates the development of BC, and that targeting BCL2 in combination with other therapeutic drugs will dramatically improve BC patients' responses to therapy and prevent the emergence of chemoresistance.