Exploring the Antioxidant Potency of New Naphthalene-Based Chalcone Derivatives: Design, Synthesis, Antioxidant Evaluation, Docking Study, DFT Calculations.

Naphthalene-based chalcone derivative was successfully synthesized through the condensation of 2,4-dichlorobenzaldehyde with 2-acetylnaphthalene. This chalcone, denoted as compound 1, demonstrated a versatile reactivity upon treatment with both nitrogen and carbon nucleophiles, and yielded diverse heterocyclic scaffolds such as pyrazoline, thiazole, pyrimidine, pyran, and pyridine derivatives. The pyrazoline aldehyde derivative 7 was further derivatized to produce the hydrazide-hydrazone 13, namely, (1H-pyrazol-1-yl)methylene)acetohydrazide, which was exploited to synthesize derivatives of 2-oxo-2H-chromene-3-carbohydrazide 14, 2-(4-oxo-4,5-dihydrothiazol-2-yl)acetohydrazide 15, and 3-(4-nitrophenyl)acrylohydrazide 16. All the newly synthesized compounds were characterized by melting point, elemental analysis, as well as FT-IR, 1 H-NMR and mass spectroscopy. Furthermore, these heterocyclic derivatives were screened for their antioxidant capacities using the DPPH radical assay. The results showed that compounds 5 and 10 are the most potent antioxidants with IC50 values 178, 177(µM), respectively. comparable to that of ascorbic acid which has IC50 value 148. Meanwhile, compounds 2, 12, 13, 14, 15, and 16 exhibited moderate antioxidant activities with IC50 values ranged from 266 to 291(µM). Thus, these heterocycles could emerge as promising antioxidant drugs for the treatment of oxidative stress-related diseases. Finally, molecular docking was conducted to study the binding affinity for the most potent antioxidant compounds 5, 10, and ascorbic acid inside the active pocket of Human Peroxiredoxin 5 (1HD2). DFT calculations and global descriptors were calculated for the most potent compounds to correlate the relation between chemical structure and reactivity.

One-pot synthesis, computational chemical study, molecular docking, biological study, and in silico prediction ADME/pharmacokinetics properties of 5-substituted 1H-tetrazole derivatives.

An efficient synthesis of 5-substituted 1H-tetrazoles was successfully achieved through one-pot multi-component condensation reactions of some aromatic aldehydes or indolin-2,3-dione with malononitrile and sodium azide using diverse reaction conditions to obtain considerable product yields. Furthermore, it has been achieved for the first time to construct desired products under neat condition. Molecular docking studies with CSNK2A1 receptor disclosed the lowest binding energy displayed by the dimethoxyphenyl derivative 4c with - 6.8687 kcal/mol. The synthesized tetrazoles were screened for their in-vitro cytotoxic activity against epidermoid cancer cell line (A431) and colon cancer line (HCT116) with respect to normal skin fibroblast cell line (BJ-1) using MTT assay, and antimicrobial activity against the bacteria: K. pneumonia, S. aureus, and the fungi: Candida albicans, as well as their antioxidant activity using 2,2-diphenyl-1-picrylhydrazyl assay. In addition, the toxicity of tetrazole derivative was assessed by determination of their approximate lethal dose fifty (LD50), calculated via an oral administration to rats, through measurement of ALT and bilirubin levels in serum. The antitumor results can suggest that the potent tetrazole derivative namely, 3-(3,4-dimethoxyphenyl)-2-(1H-tetrazol-5-yl)acrylonitrile (4c) could be a potential drug against epidermoid carcinoma. The antioxidant results indicated to tetrazoles exhibited great antioxidant properties even at very low doses. A molecular dynamics simulation was performed for the synthesized compounds (ligands) to investigate their tendency for binding with the active sites of protein.

Synthesis, Antioxidant and Antiproliferative Evaluation, Molecular Docking and DFT Studies of Some Novel Coumarin and Fused Coumarin Derivatives.

N'-[(4-Chloro-2-oxo-2H-chromen-3-yl)methylene]-2-cyanoacetohydrazide (3) was synthesized in excellent yield from the condensation of 4-Chloro-2-oxo-2H-chromene-3-carbaldehyde with cyanoacetohydrazide. Compound 3 was utilized as a building block to synthesize novel coumarin and heterocycle-fused coumarin derivatives. The chemical structures of all the new coumarin compounds were identified by spectral analyses. Some of the new coumarins compounds were screened in human cancer cell lines (HEPG-2, MCF-7, HCT-116 and PC-3) to learn about their cytotoxic effects in addition to the study of their DNA damage and antioxidant activity. Three of these compounds exhibited remarkable antioxidant and anti-proliferative activities. Moreover, they have the capability to protect DNA from damage induced by bleomycin. Molecular docking, DFT and molecular electrostatic potential studies were performed on the compounds in vitro.

Synthesis, DFT, and eco-friendly insecticidal activity of some N-heterocycles derived from 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one.

A new series of nitrogen heterocycles encompassing a quinoline scaffold such as imidazolone, benzimidazole, triazinone, triazole, and thiazole derivatives was synthesized utilizing the readily obtainable building block synthon, 4-((2-oxo-1,2-dihydroquinolin-3-yl)methylene)-2-phenyloxazol-5(4H)-one (3). It was interesting that the fused heterocycle, pyranoquinoline derivative 15 was successfully synthesized by different routes of reactions. The synthesized compounds were evaluated for their insecticidal activity and compounds 6, 17, and 20 were the most potent against both Mythimna separata and Nilaparvata lugens. The DFT study was performed for the most potent compounds.