Synthesis of novel benzimidazole acrylonitriles for inhibition of Plasmodium falciparum growth by dual target inhibition

Antimalarial drug resistance has emerged as a threat for treating malaria, generating a need to design and develop newer, more efficient antimalarial agents. This research aimed to identify novel leads as antimalarials. Dual receptor mechanism could be a good strategy to combat developing drug resistance. A series of benzimidazole acrylonitriles containing 18 compounds were designed, synthesized and evaluated for cytotoxicity, heme binding, ferriprotoporphyrin IX biomineralisation inhibition, and falcipain-2 enzyme assay. Furthermore, in silico docking and MD simulation studies were also performed.The tests revealed quite encouraging results. Three compounds, viz. R-01 (0.69 μM), R-04 (1.60 μM), and R-08 (1.61 μM), were found to have high antimalarial activity. These compounds were found to be in bearable cytotoxicity limits and their biological assay suggested that they had inhibitory activity against falcipain-2 and hemozoin formation. The docking revealed the binding mode of benzimidazole acrylonitrile derivatives and MD simulation studies revealed that the protein-ligand complex was stable. The agents exhibit good hemozoin formation inhibition activity and, hence, may be utilized as leads to design a newer drug class to overcome the drug resistance of hemozoin formation inhibitors such as chloroquine

Antibacterial nanoparticles based on fluorescent 3-substituted uridine analogue

With a sudden and rapid increase in the spread of antimicrobial resistance, there is an urgent need for the development of novel antimicrobial therapies. Nanoparticles with antimicrobial activity provide advantages such as improved solubility, permeability, stability and selectivity. In this study, a uridine-scaffold was connected to a pyrene fluorescent unit to obtain novel compound UPy via an economical and straightforward route. Further, fluorescent organic nanoparticles (FONs) were prepared via self assembly of UPy and were found to have antibacterial activity towards Gram positive bacteria. The fluorescent nature of the FONs allowed us to identify a binding partner and propose mechanism of action in vivo. We believe that UPy can be an excellent starting point for the development of novel, potent and selective antimicrobial nanotherapeutics

AgNO3 mediated C-N bond forming reaction: synthesis of 3-substituted benzothiazines as potential COX inhibitors

AgNO facilitated the intramolecular ring closure of o-(1-alkynyl)benzenesulfonamides via a regioselective C-N bond forming reaction leading to the formation of 3-substituted benzothiazine derivatives. A number of compounds were prepared in good yields by using this inexpensive and safe methodology. All the compounds synthesized were evaluated for their cyclooxygenase (COX) inhibiting properties in vitro. A number of compounds that do not contain an enolic hydroxyl group showed selectivities toward COX-2 over COX-1 inhibition. This was further supported by the predictive binding mode of two compounds with COX-1 and -2 proteins through molecular docking studies

Synthesis of some coumarinyl chalcones and their antiproliferative activity against breast cancer cell lines

A series of coumarinyl chalcones derivatives were synthesized and evaluated for their antiproliferative activities on three different breast cancer cell lines (MDA-MB231, MDA-MB468, MCF7) and one non-cancer breast epithelial cell line (184B5). The coumarinyl derivatives exhibited anticancer activity against breast cancer cell lines at a micromolar range. A structure-activity relationship (SAR) analysis was performed by studying the effect of substituents on their antiproliferative activities. One of the compound 3i bearing methoxy substitutions at the R1, R2 and R3 positions of the phenyl ring showed comparable potency to the reference drug cisplatin as well as a two-fold higher selectivity for the breast cancer cell lines than 184B5 cells