Huda A. Al-Ghamdi

In the current study, triazolo pyrimidine coumarin and benzocoumarin derivatives were prepared using green methods as a fast and cost-efficient strategy in comparison with the traditional method in terms of reaction time and yield. Combining coumarins with other bioactive compounds could improve the anticancer properties and other biological activities. Therefore, both compounds were evaluated in silico as potential early-stage small molecule inhibitors of three targets, which cause four life-threatening diseases: leukaemia FLT3 (PDB: 4XUF), SARS-COV-2 (3CLpro) (PDB: 6M2N), and adenosine A1 receptors A1R (PDB: 5N2S), which could cause heart failure and Alzheimer’s disease. It was discovered that both compounds show promising results against the three targets. However, benzocoumarin shows an advantage over coumarin compounds. The effects of modifications to the coumarin core have been studied using an in silico technique that evaluates pharmacokinetics, absorption, distribution, metabolism, excretion, and toxicity of these compounds, showing promising results as an early-stage drug. However, both compounds were predicted to be highly absorbed from the gastrointestinal tract and enter the blood-brain barrier efficiently. The predicted oral toxicity of both compounds was LD50 = 350 mg/kg, putting both of them in the IV toxicity class. The optical properties of coumarin and benzocoumarin compounds were also investigated. Graphical abstract

Heterocyclic compounds have shown that they hold significant therapeutic activities, highlighting the importance of discovering and developing novel candidates against cancers, infections, and oxidative stress-associated disorders. In this study, we demonstrated the biological activity of our previously synthesized thiazolidinone derivatives (TZDs-1, 6, and 7). Furthermore, we synthesized and structurally characterized a new derivative (TZD-5) using IR, ¹H NMR, and ¹³C NMR spectroscopy, confirming the presence of its key functional groups, namely, carbonyl and imine. Their antioxidant activity was assessed through the DPPH assay, with TZD-5 showing the most potent effect (IC₅₀ = 24.4 µg/mL), comparable to ascorbic acid, an effect attributed to the methoxy group introduced via N-alkylation. Cytotoxicity was evaluated using the MTS assay on normal (HFF-1) and cancerous (HepG2 and A549) cell lines at two time points: 24- and 48 h exposure. Our findings highlight clear differences in cytotoxicity and selectivity among the tested thiazolidinone derivatives. TZD-1 and TZD-6 demonstrated significant, dose-dependent cytotoxic effects on both cancerous (HepG2 and A549) and normal (HFF-1) cell lines, thus limiting their therapeutic potential due to insufficient selectivity. TZD-5 exhibited moderate selectivity with higher susceptibility for HepG2 cells compared to normal cells. Notably, TZD-7 showed the most favorable cytotoxic profile, demonstrating strong selective cytotoxicity toward cancer cell lines with minimal adverse effects on normal fibroblasts. Overall, the results highlight TZD-5 and TZD-7 as promising candidates for antioxidant and selective anticancer therapies.

Imidazole derivatives are considered potential chemical compounds that could be therapeutically effective against several harmful pathogenic microbes. The chemical structure of imidazole, with a five-membered heterocycle, three carbon atoms, and two double bonds, tends to show antibacterial activities. In the present study, novel imidazole derivatives were designed and synthesized to be evaluated as antimicrobial agents owing to the low number of attempts to discover new antimicrobial agents and the emerging cases of antimicrobial resistance. Two imidazole compounds were prepared and evaluated as promising candidates regarding in vitro cytotoxicity against human skin fibroblast cells and antimicrobial activity against several bacterial strains. The synthesized imidazole derivatives were chemically identified using nuclear magnetic resonance (NMR) and Fourier-transform infrared spectroscopy (FTIR). The results demonstrated a relatively high cell viability of one of the imidazole derivatives, i.e., HL2, upon 24 and 48 h cell exposure. Both derivatives were able to inhibit the growth of the tested bacterial strains. This study provides valuable insight into the potential application of imidazole derivatives for treating microbial infections; however, further in vitro and in vivo studies are required to confirm their safety and effectiveness.

We synthesized 1,3,5-triyltris((4-chlorophenyl)methanone) by a condensation reaction in glacial acetic acid and studied utilizing spectroscopic and analytical techniques such as ultraviolet, infrared, mass, elemental, and nuclear magnetic resonance (NMR) spectroscopy, as well as X-ray crystallography. The effect of chlorine substitution in the 1,3,5-triaroylbenzene compound in solid-state arrangements was studied. Halogen bonds are detected in the solid-state structures of the titled compound. A dimeric structure is formed due to the presence of two C-Cl···Cl Type I halogen interactions. Additionally, a delocalized Type III C-Cl···π interaction were reported. C-Cl···H hydrogen bonding and π···π interaction were also reported. Hirshfeld surface analysis, 3D fingerprint, the energy framework, and the electro-optic potential were used to evaluate such interactions.

The fundamentals of Pd-catalyzed Csp²−Csp² Miyaura borylation, Suzuki cross-coupling, and Stille cross-coupling reactions for a variety of borylated precursors based on phenothiazine (PTZ), phenoxazine (POZ), carbazole (Cz), and quinoxaline (QX) units have been explored. Three palladium-based catalysts were chosen for this study: Pd(PPh₃)₄, Pd(PPh₃)₂Cl₂, and Pd(dppf)Cl₂, applying different reaction conditions. Around 16 desired chromophores were successfully designed and synthesized using C-C cross-coupling reactions in moderate to excellent yields, including PTZ, POZ, and Cz units coupled with QX, indolinium iodide, thienyl, phenyl, or triphenylamine moieties. Additionally, PTZ, POZ, and Cz have been employed in synthesizing various pinacol boronate ester derivatives in good to moderate yields. Interestingly, Pd(dppf)Cl₂ was found to be the best catalyst for borylation, and C-C cross-coupling reactions occurred in as little as 30 min, with an excellent yield exceeding 98%. Pd(PPh₃)₄ and Pd(PPh₃)₂Cl₂ catalyzed the reaction to obtain the desired products in moderate to good yields after a long time (20–24 h). On the other hand, the Suzuki-Miyaura cross-coupling between N-(2-methyl)hexyl carbazole pinacol boronate ester derivative 10c and three halogenated quinoxaline derivatives—4-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)benzaldehyde (27), 4-(5-(3-(5-bromothiophen-2-yl)quinoxalin-2-yl)thiophen-2-yl)benzaldehyde (30), and 4-(3-chloroquinoxalin-2-yl)benzaldehyde (25) catalyzed by Pd(PPh₃)₄—afforded three carbazole-quinoxaline chromophores (28, 30, and 31, respectively) in 2–3 h, with good to excellent yields reaching 86%. The electron-deficient QX couplers proved to be coupled efficiently using the Stille coupling reaction, which involves the coupling between electron-rich orgaostannane and electron-deficient halide. The synthesized precursors and desired chromophores were characterized by FTIR, ¹H-NMR, ¹³C-NMR, and HRMS.

In the study reported in this manuscript, silver/iron oxide nanocomposites (Ag/Fe₂O₃) were phytosynthesized using the extract of Buddleja lindleyana via a green, economical and eco-friendly strategy. The biosynthesized Ag/Fe₂O₃ nanocomposites were characterized using UV-Vis spectrophotometry, FTIR, XRD, TEM, DLS and SEM-EDX analyses. The particulates showed a triangular and spherical morphology having sizes between 25 and 174 nm. FTIR studies on the nanoparticles showed functional groups corresponding to organic metabolites, which reduce and stabilize the Ag/Fe₂O₃ nanocomposite. The antimicrobial efficacy of the phytosynthesized Ag/Fe₂O₃ against bacterial pathogens was assessed. In addition, Ag/Fe₂O₃ exhibited broad spectrum activities against B. subtilis, S. aureus, E. coli, and P. aeruginosa with inhibition zones of 23.4 ± 0.75, 22.3 ± 0.57, 20.8 ± 1.6, and 19.5 ± 0.5 mm, respectively. The Ag/Fe₂O₃ composites obtained showed promising antibacterial action against human bacterial pathogens (S. aureus, E. coli, B. subtilis and P. aeruginosa), making them candidates for medical applications.