Synthesis, Docking, Computational Studies, and Antimicrobial Evaluations of New Dipeptide Derivatives Based on Nicotinoylglycylglycine Hydrazide.

Within a series of dipeptide derivatives (5-11), compound 4 was refluxed with d-glucose, d-xylose, acetylacetone, diethylmalonate, carbon disulfide, ethyl cyanoacetate, and ethyl acetoacetate which yielded 5-11, respectively. The candidates 5-11 were characterized and their biological activities were evaluated where they showed different anti-microbial inhibitory activities based on the type of pathogenic microorganisms. Moreover, to understand modes of binding, molecular docking was used of Nicotinoylglycine derivatives with the active site of the penicillin-binding protein 3 (PBP3) and sterol 14-alpha demethylase's (CYP51), and the results, which were achieved via covalent and non-covalent docking, were harmonized with the biological activity results. Therefore, it was extrapolated that compounds 4, 7, 8, 9, and 10 had good potential to inhibit sterol 14-alpha demethylase and penicillin-binding protein 3; consequently, these compounds are possibly suitable for the development of a novel antibacterial and antifungal therapeutic drug. In addition, in silico properties of absorption, distribution, metabolism, and excretion (ADME) indicated drug likeness with low to very low oral absorption in most compounds, and undefined blood-brain barrier permeability in all compounds. Furthermore, toxicity (TOPKAT) prediction showed probability values for all carcinogenicity models were medium to pretty low for all compounds.

Design, synthesis and anticancer activity of novel pyrimidine and pyrimidine-thiadiazole hybrid glycosides.

New 1,3,4-thiadiazole thioglycosides linked to substituted pyrimidines were synthesized via glycosylation of 1,3,4-thiadiazole thiol compounds. Also, novel 1,2,3-triazole derivatives linked to carbohydrate units were prepared using the standard click chemistry conditions employing the Cu(I)-catalyzed azide-alkyne cycloaddition of substituted-aryl-azides with a selection of alkyne-functionalized sugars. The chemical structures of the new derivatives were verified using various spectroscopic techniques, such as IR, 1H NMR, 13C NMR and elemental analyses. The cytotoxic activities of the prepared compounds were investigated in vitro against human liver cancer (HepG-2) and human breast adenocarcinoma (MCF7) cell lines. In addition, the biological evaluation of the new compounds involved the investigation of their effects on a human normal retinal pigmented epithelial cell line (RPE1) using the MTT assay.

In vitro anticancer potentiality and molecular modelling study of novel amino acid derivatives based on N1,N3-bis-(1-hydrazinyl-1-oxopropan-2-yl) isophthalamide.

A series of N1,N3-bis (1-oxopropan-2-yl) isophthalamide-based derivatives 4-16 were prepared and their structures were confirmed by different spectral tools. The cytotoxic potentiality of novel compounds 4-16 was assessed by the MTT assay method on colon, lung and breast tumour cell lines. Compound 5 gave the most significant specificity anticancer activity with safety response on normal cell lines. In vitro enzyme assay and several apoptotic parameters were examined to elucidate the mode of action of compound 5. Molecular docking studies also were simulated to put insight and give better understanding to its structural features.

Triazolopyrimidines and Thiazolopyrimidines: Synthesis, Anti-HSV-1, Cytotoxicity and Mechanism of Action.

BACKGROUND: Several commercial drugs utilized in the treatment of HSV containing pyrimidine moiety. Because of the ineffectiveness of virus drugs due to the resistance of the patient's immune system, there is a pressing need to prepare new compounds that are effective in the treatment of various viruses. RESULTS: Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. The structure of all prepared compounds was characterized by their spectroscopic data and also, their ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%. Furthermore, the selectivity indices of the tested compounds are high and have weak cytotoxicity (all samples were checked, not chosen on cytotoxicity basis, we only utilize secure concentrations of every compound). CONCLUSION: We succeeded in this context to synthesize a new series of potent fused pyrimidine derivatives as anti-HSV-1.