To develop new antimicrobial agents, a series of novel thiourea derivatives incorporated with different moieties 2–13 was designed and synthesized and their biological activities were evaluated. Compounds 7a, 7b and 8 exhibited excellent antimicrobial activity against all Gram-positive and Gram-negative bacteria, and the fungal Aspergillus flavus with minimum inhibitory concentration (MIC) values ranged from 0.95 ± 0.22 to 3.25 ± 1.00 μg/mL. Furthermore, cytotoxicity studies against MCF-7 cells revealed that compounds 7a and 7b were the most potent with IC50 values of 10.17 ± 0.65 and 11.59 ± 0.59 μM, respectively. On the other hand, the tested compounds were less toxic against normal kidney epithelial cell lines (Vero cells). The in vitro enzyme inhibition assay of 8 displayed excellent inhibitory activity against Escherichia coli DNA B gyrase and moderate one against E. coli Topoisomerase IV (IC50 = 0.33 ± 1.25 and 19.72 ± 1.00 µM, respectively) in comparison with novobiocin (IC50 values 0.28 ± 1.45 and 10.65 ± 1.02 µM, respectively). Finally, the molecular docking was done to position compound 8 into the E. coli DNA B and Topoisomerase IV active pockets to explore the probable binding conformation. In summary, compound 8 may serve as a potential dual E. coli DNA B and Topoisomerase IV inhibitor.

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A new series of heterocyclic Schiff base complexes derived from the condensation of nicotinohydrazide with different heterocyclic aldehyde, followed by metalation with Co (II) and Cu (II) metal ions. The chemical structures of the synthesized compounds have been characterized by elemental analysis, Fourier transform infrared spectroscopy, proton nuclear magnetic resonance, ultraviolet–visible spectroscopy, and magnetic susceptibility. The spectral and magnetic data confirmed their chemical structures, furthermore, the geometry of Cu (II) and Co (II) complexes were square‐planar or distorted tetrahedral. X‐ray diffraction measurements supported the crystalline structures of the metal complexes rather than the amorphous form of the parent Schiff bases. Thermogravimetric analysis revealed the upgrading of the thermal stability of metal complexes compared to their Schiff base ligands. Antimicrobial efficacies of the Schiff base ligands and their corresponded metal complexes were screened against Staphylococcus aureus and Bacillus subtilis as Gram‐positive bacteria, Escherichia coli, and Proteus vulgaris as Gram‐negative bacteria, and fungi Aspergillus flavus, Candida albicans. The antimicrobial inhibitory data revealed higher antimicrobial activities of metal complexes compared to their Schiff base ligands. Density functional theory module by Gaussian 09 W software proved the chemical reactivity of the prepared Schiff base ligands based on the total energy, energy gap, EHOMO, and ELUMO energies.

A new series of benzimidazole, 1,2,4-triazole, and 1,3,5-triazine derivatives were designed and synthesized using a microwave irradiation synthetic approach utilizing 2-phenylacetyl isothiocyanate (1) as a key starting material. All the new analogues were evaluated as anticancer agents against a panel of cancer cell lines utilizing doxorubicin as a standard drug. Most of the tested derivatives exhibited selective cytotoxic activity against MCF-7 and A-549 cancer cell lines. Furthermore, the new target compounds 5 , 6 , and 7 as the most potent antiproliferative agents have been assessed as in vitro EGFR WT and EGFR T790M inhibitors compared to the reference drugs erlotinib and AZD9291. They represented more potent suppression activity against the mutated EGFR T790M than the wild-type EGFR WT . Moreover, the compounds 5 , 6 , and 7 down-regulated the oncogenic parameter p53 ubiquitination. A docking simulation of compound 6b was carried out to correlate its molecular structure with its significant EGFR inhibition potency and its possible binding interactions within the active site of EGFR WT and the mutant EGFR T790M .

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