Abd-Allah Sh. El-Etrawy

This study reports the synthesis and comprehensive characterization of a new series of 1,2,4-triazolo[4,3-a] pyrimidin-5-(1 H )-one derivatives. These compounds were synthesized from 2-hydrazinopyrimidines via cyclization reactions. Density Functional Theory (DFT) calculations revealed the molecular structures, stability, and electronic properties of the derivatives. Computational studies revealed that the compounds exhibited planar conformations, though the triazole rings were found to be non-coplanar with the pyrimidine ring. Substituents like methyl, amino, and propyl groups influenced bond lengths, dihedral angles, and electronic properties. Binding energies confirmed molecular stability, while IR spectra supported dynamical stability. UV-Vis’s absorption spectra matched experimental data, showing maxima in the 250–400 nm range, with redshifts attributed to electron-donating substituents. Density of State (DOS) and HOMO/LUMO analyses indicated strong orbital interactions and electron delocalization. Molecular docking studies suggested favorable binding with the DNA gyrase receptor, indicating potential antimicrobial activity against both Gram-positive and Gram-negative bacteria. This study provides valuable insights into the synthesis, structural, electronic, and antimicrobial properties of 1,2,4-triazolo[4,3-a] pyrimidin-5-(1 H )-one derivatives, highlighting their potential applications in medicinal chemistry and materials science.

Cancer is a disease that can be fatal everywhere. It can start in almost any organ or tissue of the body when abnormal cells grow uncontrollably; they go further than their usual boundaries to attack contiguous parts of the body and/or slap-up meal to other organs. The primary problem facing current treatment techniques, such as chemotherapy and radiation, is multidrug resistance (MDR). Finding a unique and varied structural framework could open the door to the creation of fresh, potent anticancer medications. Also, the knowledge in genomics and molecular sciences has helped in creating new drug targets. Pyrimidines, a class of nitrogen-containing heterocyclic compounds, play a significant role in crafting cancer treatment drugs. These synthetic compounds have proven effective against various cancers, including myeloid leukemia, breast cancer, liver cancer, pancreatic cancer, and idiopathic pulmonary fibrosis. This review presents the findings of several investigations conducted between 2006 and 2023 on pyrimidine derivatives and their corresponding anticancer characteristics.

Due to numerous pharmaceutical and biological activities hydrazone (TC) based materials, it was important to investigate quantum chemical studies such as Density functional theory (DFT) calculations, natural bond orbital (NBO) analysis, molecular electrostatic potential (MESP), and local reactivity usage Fukui function for six TC derivatives compounds. DFT, NBO, MESP, and local reactivity calculations were obtained via utilizing CAM-Becke's three-parameter functional and Leee Yange Parr (CAM-B3LYP) functional and 6-311G + + (2d, 2p) basis set. Optimized molecular structures for all studied compounds were obtained usage the DFT/CAM-B3LYP/6-311G + + (2d, 2p) method. In addition, the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), energy gap (E_g), light harvest efficiency (LHE), and open-circuit voltage (Voc) of all studied MSs are calculated and illustrated. These properties indicate that these molecular modeling structures as good candidates for utilization in organic DSSCs. The calculated spectroscopic investigations of hydrazine derivatives have been obtained by applying the TD/CAM-B3LYP/6-311G + + (2d, 2p) method. the calculated UV–Vis absorption spectra for molecular structures under study show nice correlations with experimental spectra.

A series of new 2‐arylbenzimidazole‐ N ‐1 acetamido conjugates have been synthesized and characterized. Their antifungal activities were evaluated against fluconazole‐resistant C. albicans and A. fumigatus by the inhibition zone technique and were compared with the standard amphotericin B. Minimum inhibitory concentrations were determined for the most potent compounds, after preliminary structure‐activity analysis. Based upon these results a sub‐set of twelve ethylglycinyl ester conjugates bearing fluoro, chloro or bromo substituents on the 2‐phenyl moiety were examined for structure‐activity relationships using an agarose diffusion method employing a hypersensitive Sacharomyces cerevisiae strain. None of these compounds however showed significant activity at the concentrations tested. Single‐crystal X‐ray determinations were conducted on two of the newly synthesized compounds and were compared with DFT computational analysis.

A series of 2‐oxo‐2,5‐dihydro‐1H‐chromeno[4,3‐b]pyridine derivatives were obtained by using a one‐pot three component reaction of 2,2‐disubstituted chroman‐4‐one with aromatic aldehydes and 2‐cyanoacetamide in the presence of sodium hydroxide under solvent‐free conditions. Heating chromenopyridine derivatives with phosphoryl chloride gave the corresponding chloro derivatives. The reaction of the chloro derivatives with hydrazine hydrate afforded dihydrochromeno[4,3‐b]pyrazolo[4,3‐e]pyridines derivatives. Condensation of the dimethyl derivative compound with the aromatic aldehydes gave 8‐Arylideneamino‐6,6‐dimethyl‐10H‐chromeno[4,3‐b]pyrazolo[4,3‐e]pyridine.

Abstract: Novel 5,6-disubstituted pyridazin-3(2H)-one derivatives were designed and synthesized as combretastatin A-4 analogues. Our objective was to overcome the spontaneous cis to trans isomerization of the compound. We therefore replaced the cis-double bond with a pyridazine ring. The antiproliferative activity of the novel analogues was evaluated against four human cancer cell lines (HL-60, MDAMB- 435, SF-295 and HCT-8). We found that the analogues had little activity either against selected cell lines or against purified tubulin. Molecular modeling studies may account for their inactivity.

Several synthetic strategies were developed for the preparation of highly substituted pyrido[2,3-d]pyridazines. We particularly focused on the impact of the pyridine nitrogen atom on pyridazine ring reactivity toward aromatic substitutions, alkylations, or pallado-catalyzed cross-coupling reactions.