Leishmaniasis being one of the six major tropical diseases that affects nearly 0.7-1.3 million people annually, has so far limited and high toxic therapeutic options. Herein, we report the synthesis, in silico, and in vitro evaluations of novel coumarin-incorporated isatin hydrazones (Spf-1 – Spf-10) as highly potent and safe antileishmanial agents. Molecular docking was initially carried out to decipher the binding confirmation of lead molecules towards the active cavity of the target protein (Leishmanolysin gp63) of Leishmania tropica. Among all the docked compounds, only Spf-6, Spf-8, and Spf-10 showed high binding affinities due to a pattern of strong conventional hydrogen bonds and hydrophobic π-interactions. The molecular dynamics simulations showed the stable pattern of such bonding and structure-based confirmation with a time scale of 50 ns towards the top compound (Spf-10) and protein. These analyses affirmed the high stability of the system. Three out of ten compounds evaluated for their antileishmanial activity against Leishmania tropica promastigotes and amastigotes were found to be active at micromolar concentrations (IC50 range 0.1-4.13 μmol/L), and most importantly, they were also found to be highly biocompatible when screened for their toxicity in human erythrocytes.Tropical theileriosis is among the most common vector-borne diseases and caused by Theileria parasites. Theileria annulata is an obligate intracellular protozoan parasite and transmitted to especially Bos taurus and Bos indicus by Hyalomma tick vectors. C8 ([4-(3,4-dimethoxyphenyl)-6,7-dihydroxy-2H-chromen-2-one); C9 (4-(3,4-dihydroxyphenyl)-7,8 dihydroxy-2H-chromen-2-one); C21 (4-(3,4-dihydroxyphenyl)-6,7-dihydroxy-2H-chromen-2 one) were identified as potent Theileria annulata enolase (TaEno) inhibitors in our previous studies. An ideal drug compound must inhibit the target parasite enzyme without inhibiting its homolog in the host. In this study, the inhibitory effect of the compounds previously evaluated on TaEno were tested on the host Bos taurus enolase (BtEno3) by in vitro studies. The interactions of enzyme-coumarin and enzyme-coumarin-substrate by in silico studies were also performed. selleck inhibitor All of the coumarin derivatives tested showed very low inhibitory effects on B. taurus enolase; 36,87% inhibition at 100 μM concentration for C8, 8,13% inhibition at 100 μM concentration for C9 and 77,69 μM of IC50 value for C21. In addition, these three coumarin derivatives and substrate 2PG were docked into the BtEno3 using molecular docking methods. Molecular interactions between enolase-coumarin and enolase-coumarin-substrate complexes were analyzed using molecular dynamics simulation methods for 100 ns. Estimated free energy of bindings of the substrate 2PG and coumarin derivatives to the BtEno3 were calculated by MM-GB(PB)SA methods. In comparison to the inhibition studies performed on TaEno, C8 and C9 coumarin derivatives remain the possible inhibitor candidates as they inhibit the host enolase at very high concentrations. These two promising compounds will be further analyzed by in vitro and in vivo studies towards developing an alternative drug against tropical theileriosis.Twenty novel 7-benzyloxycoumarin based compounds were synthesized with a variety of bioactive chemical fragments. The synthesized compounds showed remarkable acetylcholinesterase (AChE) inhibitory activity. In vitro assay revealed that compounds 7-benzyloxy-4-[(4-phenylthiazol-2(3H)-ylidene)hydrazono]methyl-2H-chromen-2-one (5b, IC50= 0.451μM), 7-benzyloxy-4-([4-(4-methoxyphenyl)thiazol-2(3H)-ylidene]hydrazonomethyl)-2H-chromen-2-one (5d, IC50= 0.625μM), 5-amino-1-[2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)acetyl]-1H-pyrazole-4-carbonitrile (13c, IC50= 0.466μM), 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-(2-methylimino-4-phenylthiazol-3(2H)-yl)acetamide (16a, IC50= 0.500μM) and 2-(7-benzyloxy-2-oxo-2H-chromen-4-yl)-N-[4-(4-methoxyphenyl)-2-methyliminothiazol-3(2H)-yl]acetamide (16b, IC50= 0.590μM) exhibited promising AChE inhibitory activity even better than donepezil (IC50= 0.711μM). Kinetic study for compound 5b implied mixed type inhibitor which could bind peripheral anionic site (PAS) and catalytic active site (CAS) of AChE enzyme. In addition, in vivo evaluation of compounds 5b, 13c and 16a confirmed significant memory improvement in scopolamine-induced impairment model in tested mice. Furthermore, in silico studies were performed on the synthesized compounds which included molecular docking study at the active site of recombinant human acetylcholinesterase enzyme (rhAChE) as well as prediction of ADMET and other physicochemical parameters. A correlation between the docking results and IC50 of tested compounds was routinely observed and shared similar binding pattern to the co-crystallized ligand donepezil.Many studies have investigated how trehalose glycolipid structures can be modified to improve their Macrophage inducible C-type lectin (Mincle)-mediated adjuvanticity. However, in all instances, the ester-linkage of α,ά-trehalose to the lipid of choice remained. We investigated how changing this ester-linkage to an amide influences Mincle signalling and agonist activity and demonstrated that Mincle tolerates this functional group change. In in vivo vaccination studies in murine and ovine model systems, using OVA or Mannheimia haemolytica and Mycoplasma ovipneumoniae as vaccine antigens, respectively, it was demonstrated that a representative trehalose diamide glycolipid was able to enhance antibody-specific immune responses. Notably, IgG titres against M. ovipneumoniae were significantly greater when using trehalose dibehenamide (A-TDB) compared to trehalose dibehenate (TDB). This is particularly important as infection with M. ovipneumoniae predisposes sheep to pneumonia.Aminoacyl-tRNA synthetases (aaRSs) are crucial for the correct assembly of amino acids to cognate tRNA to maintain the fidelity of proteosynthesis. AaRSs have become a hot target in antimicrobial research. Three aaRS inhibitors are already in clinical practice; antibacterial mupirocin inhibits the synthetic site of isoleucyl-tRNA synthetase, antifungal tavaborole inhibits the editing site of leucyl-tRNA synthetase, and antiprotozoal halofuginone inhibits proline-tRNA synthetase. According to the World Health Organization, tuberculosis globally remains the leading cause of death from a single infectious agent. The rising incidence of multidrug-resistant tuberculosis is alarming and urges the search for new antimycobacterial compounds, preferably with yet unexploited mechanism of action. In this literature review, we have covered the up-to-date state in the field of inhibitors of mycobacterial aaRSs. The most studied aaRS in mycobacteria is LeuRS with at least four structural types of inhibitors, followed by TyrRS and AspRS.