Objectives: Nowadays, antimicrobial resistance represents one of the most significant challenges in the medical community. To overcome the problem, it requires the discovery of newer safe and effective molecules against infectious sickness. Synthesis and screening of 1,8-naphthyridines have attracted much attention over the decades since it plays a key role against the microorganisms. Methods: 1,8-naphthyridine based 5-arylidene derivatives of thiazolidinone (3a-i) has been achieved by the cyclization reaction of 2-chloro-N- (2-phenyl-1,8-naphthyridin-3-yl)acetamide (1) with potassium thiocyanate in acetone followed by its Knoevenagel condensation reaction with appropriate arylaldehydes in ethanol. All the resulting products were confirmed using spectral and physicochemical data. Antibacterial activity was performed against different bacterial strains by agar disc diffusion method using ciprofloxacin as standard. Results: Compound 3b showed tremendous antibacterial activity among all the tested compounds. Conclusions: This study provides several advantages such as shorter reaction times, clean product, and good yields. Most of the final products possessed moderate to excellent antibacterial activity.

In an attempt to discover the new antibacterial agents to fight the bacterial infections, a series of 1,8-naphthyridine based 2-iminothiazolidin-4-one derivatives was synthesized by a straight-forward regioselective synthesis. 2-Phenyl-1,8-naphthyridin-3-amine (2) was reacted with acetyl or aroyl isothiocyantes to give the corresponding N-[(2-phenyl-1,8-naphthyridin-3-yl)carbamothioyl)]acetamide or benzamides (3a-e). Finally, the target compounds [N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazolidin-2-ylidene)]acetamide or benzamides (4a-e) were obtained by the reaction of thiourea (3a-e) with chloroacetyl chloride in presence of pyridine. All the synthesized products were formed in good yields and their structures were characterized by spectral (IR, EI-MS and NMR) and physical data. The biological activity of title compounds was evaluated against the bacterial strains and found to be more potent.

Pim-3 (proviral integration site moloney murine leukemia virus-3) is an oncogene which encodes proteins belonging to serine/threonine kinase family, and PIM subfamily. It is generally over expressed in epithelial and hematological tumors. It is known to involve in numerous cellular functions such as cell growth, differentiation, survival, tumorigenesis and apoptosis. It also plays a crucial role in regulation of signal transduction cascades. Therefore it emerged as a hopefultherapeutic target for cancer treatment. In current study, indole derivatives having potent inhibitory activity against Pim 3 were taken and pharmacophore based virtual screening was carried out. A five point pharmacophore hypothesis with one hydrogen bond acceptor, one hydrogen bond donor and three aromatic rings i.e., ADRRR was developed with acceptable R2and Q2 values of 0.913 and 0.748 respectively. It was employed as a query and screening was conducted against Asinex and Otava lead library databases to screen out potent drug like candidates. The obtained compounds were subjected to SP, XP docking using 3D model of pim-3 which was constructed through comparative homology modelling and finally binding free energies were calculated for top hits. The docking and binding free energy studies revealed that six hit molecules showed higher binding energy in comparison to the best active molecule. Finally, MD simulations of the top hit with highest binding energy was carried out which indicated that the obtained hit N1 formed a stable complex with pim-3. We believe that these combined protocols will be helpful and cooperative to discover and design more potent pim-3 inhibitors in near future.

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