The burden from microbial diseases has to be addressed in an increasing pace due to multidrug resistance, causing clinical annoyance, globally. Indeed, employing eco-friendly approaches by green syntheses of nanoparticles with metals/metalloids as antibacterial compounds would be continual and cost-effective. Herein, the synthesis of silver nanoparticles (AgNPs) by aqueous extracts of the cyanobacterium Chroococcus minutus (strain, CRLSUM10), collected from the meeting point of sea and river, East coast of India, are presented; both reducing and stabilizing mediators of the synthesized AgNPs were ascertained, by characteriztion by UV–visible spectrophotometry, XRD, FTIR, SEM and SEM-EDX. Furthermore, synthesized AgNPs had a remarkable antibacterial activity at the lowest dose, 100 mg against pathogenic strains of E. coli and S. pyogenes, rendering those as novel antibacterial agents against ‘upper respiratory tract infection’.

The manifestation of bacterial UTI (Urinary Tract Infection) has been predominantly endemic, globally; eventually, the development of new UTI anti-bacterial agent(s) remains the call of the day. Herein, two series of Mannich-based 4-hydroxy coumarin derivatives, 7a-m and 8a-m were designed by suitable heterocyclic amines condensed with aldehydes. The synthesized molecules were interpreted by ¹H and ¹³C NMR spectral analyses with in vitro antibacterial studies. The compound, 4-hydroxy-3-((4-hydroxy-3-methoxyphenyl)(morpholino)methyl)-2H-chromen-2-one 8l was the significant derivative against pathogenic bacteria Staphylococcus aureus and Escherichia coli with MIC values 12.50 and 25µM, respectively. Computational assessments with the Lipinski’s rule of five, ADMET properties and molecular docking studies revealed that analogues, 7f, 7l, 8d, 8j and 8k could be potent druggable molecules with significant binding affinity towards bacterial tyrosine kinase, as target. To understand the mode of binding and intrinsic stabilities of potent receptor-ligand complexes, each system was subjected molecular dynamics simulations for 100 ns. Inter-molecular contact analysis and intrinsic hydrogen-bond stability portrayed the analogues 8l form a number of non-bonded contacts with the receptor tyrosine kinase being mostly dominated by electrostatic and hydrophobic contacts. The results from the present structure-based designing approach might be a valuable tool towards identification of a new antibacterial drug candidate(s) against UTI in near future. List of Abbreviations: 4-HC, 4-hydroxy coumarin; ADMET, absorption, distribution, metabolism, excretion, toxicity; DCE, 1,2-dichloroethane; DCM, dichloromethane; DMSO, dimethyl sulfoxide ; MD, molecular dynamics; MIC, minimum inhibitory concentration; NMR, nuclear magnetic resonance; NPT, isothermal isobaric ensembles; NVT, canonical ensembles; PCA, principal component analysis; PDB, protein data bank; Rg, radius gyration, RMSF, root mean square fluctuations RSMD, root mean square deviation; UTI, Urinary Tract Infection.

Leprosy continues to be the belligerent public health hazard for the causation of high disability and eventual morbidity cases with stable prevalence rates, even with treatment by the on-going multidrug therapy (MDT). Today, dapsone (DDS) resistance has led to fear of leprosy in more unfortunate people of certain developing countries. Herein, DDS was chemically conjugated with five phytochemicals independently as dapsone-phytochemical conjugates (DPCs) based on azo-coupling reaction. Possible biological activities were verified with computational chemistry and quantum mechanics by molecular dynamics simulation program before chemical synthesis and spectral characterizations viz., proton-HNMR, FTIR, UV and LC-MS. Thein vivoantileprosy activity was monitored using the ‘mouse-foot-pad propagation method’, with WHO recommended concentration 0.01% mg/kg each DPC for 12 weeks, and the host-toxicity testing of the active DPC4 was seen in cultured-human-lymphocytesin vitro. One-log bacilli cells in DDS-resistant infected mice footpads decreased by the DPC4, and no bacilli were found in the DDS-sensitive mice hind pads. Additionally, thein vitrohost toxicity study also confirmed that the DCP4 up to 5,000 mg/L level was safety for oral administration, since a minor number of dead cells were found in red color under a fluorescent microscope. Several advanced bioinformatics tools could help locate the potential chemical entity, thereby reducing the time and resources required forin vitroandin vitrotests. DPC4 could be used in place of DDS in MDT, evidenced fromin vivoantileprosy activity andin vitrohost toxicity study.