Herein, we report an eco-friendly synthesis of a new series of quinazolinone-based derivatives as potential PARP-1 inhibitors. The 4-quinazolinone scaffold was utilized as a bioisostere to the phthalazinone core of the reference compound Olaparib. Most of the synthesized compounds displayed appreciable inhibitory activity against PARP-1. Compound 12c showed inhibitory activity at IC₅₀ = 30.38 nM comparable to Olaparib, which has IC₅₀ = 27.89 nM. Cell cycle analysis was performed for compounds 12a and 12c, and both exhibited cell growth arrest at G2/M phase in the MCF-7 cell line. In addition, both compounds increased the programmed apoptosis compared to the control. Furthermore, molecular docking of the final compounds into the PARP-1 active site was executed to explore their probable binding modes. Also, a computational QSAR and in silico ADMET study was performed. The results of this study revealed that some of the newly synthesized compounds could serve as a new framework to discover new PARP-1 inhibitors with anti-cancer activity.

A series of benzoquinoline-employing heterocycles was synthesized by treating 3-chlorobenzo[f]quinoline-2-carbaldehyde with N-phenyl-3-methylpyrazolone, 4-aminoacetophenone, 1,2-diaminoethane, and 2-cyanoethanohydrazide. Also, pyridine, chromene, α,β-unsaturated nitrile, thiosemicarbazone, and 1,2-bis-aryl hydrazine derivatives were prepared from the cyanoethanohydrazone obtained. The DFT calculations and experiment outcomes were consistent. In vitro screening of their antiproliferative efficacy was examined against HCT116 and MCF7 cancer cell lines. The pyrazolone 2 and cyanoethanohydrazone 5 derivatives exhibited the most potency, which was demonstrated by their molecular docking towards the CDK-5 enzyme. The binding energies of compounds 2 and 5 were − 6.6320 kcal/mol (with RMSD of 0.9477 Å) and − 6.5696 kcal/mol (with RMSD of 1.4889 Å), respectively, which were near to that of co-crystallized ligand (EFP). This implies a notably strong binding affinity towards the CDK-5 enzyme. Thus, pyrazolone derivative 2 would be considered a promising candidate for further optimization to develop new chemotherapeutic agents. In addition, the ADME (absorption, distribution, metabolism, and excretion) analyses displayed its desirable drug-likeness and oral bioavailability properties.

The ongoing global threat posed by coronaviruses necessitates the urgent development of effective antiviral agents. In this study, we investigated the potential of hydroxyquinoline-pyrazole candidates as antiviral agents against a range of coronaviruses, including SARS-CoV-2, MERS-CoV, and HCoV-229E. Molecular docking studies were conducted to assess the binding affinity of the synthesized compounds to key viral proteins. The compounds were prepared via condensation reactions of a pyrazolylhydrazide derivative with 2-chloro-3-formylquinoline, yielding hydrazone and pyrrolone derivatives. The cytotoxicity of compounds was evaluated using Vero E6 cells, and their antiviral activity was assessed via plaque reduction assays and viral inhibition assays using hydroxychloroquine as a positive control antiviral drug. The results revealed promising antiviral activity of the synthesized compounds against all tested coronaviruses, with selectivity indices indicating their potential as selective antiviral agents. Notably, the compounds exhibited potent inhibition of SARS-CoV-2 at lower concentrations, highlighting their promise as therapeutic candidates against this highly pathogenic virus. Likewise, the modeling pharmacokinetics approach showed its appropriate drug-likeness and bioavailability assets. These findings underscore the importance of hydroxyquinoline-pyrazole derivatives as potential antiviral agents against diverse coronaviruses, providing valuable insights for further therapeutic development.

Pyrazolyl-substituted 2(3H)-furanone was allowed to react with different nitrogen nucleophiles such as hydrazine hydrate, ethylenediamine, ethanolamine, and anthranilic acid to give pyrrolone and benzoxazinone derivatives. The acid hydrazide 3 was reacted with some carbonyl compounds such as 4-chlorobenzaldehyde, chloroacetyl chloride, and acetic anhydride to give thiazolidinone, oxadiazole, and pyridazinone derivatives. Selected examples of the synthesized compounds were evaluated as anticancer agents against three types of carcinoma cell lines (HePG 2, HCT116, and PC3), using Doxorubicin as a reference drug. The result revealed that some of the new compounds showed high activities. Compound 6a was more potent than the standard drug. A docking study using MOE 2008.10 program was performed.

Aim: Thiophene-based heterocycles were synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli, Clostridium difficile and Ca... Plain language summary A series of thiophene-based heterocycles was synthesized and evaluated for their antimicrobial activity against methicillin-resistant Staphylococcus aureus, Escherichia coli,... Graphical abstract