Diversity oriented synthesis and SAR studies of new quinazolinones and related compounds as insecticidal agents against Culex pipiens L. Larvae and associated predator.

The ongoing study reports the synthesis, spectroscopic analyses and larvicidal efficacy of novel series of quinazolinone derivatives and related compounds. The structures of the products were confirmed relied on their analytical and spectral data (IR, 1H NMR, and 13C NMR). The spectral documentation promoted the successful isolation of the desirable compounds. The insecticidal activities of the synthesized compounds were assessed against laboratory and field strains of Culex pipiens larvae and a predator from the same ecological niche, Cybister tripunctatus. The results revealed that most of the tested compounds showed high potencies against lab strain of C. pipiens larvae with low resistance ratios in filed strain. In particular, compounds 15, 6 and 16 showed low LC50 values, 0.094, 0.106, 0.129 (µg/mL), respectively against lab strain of C. pipiens larvae. The present study also explored the toxicity of tested compounds against field strain of non-target C. tripunctatus. Most of tested compounds were safer than temephos, especially 15 and 6 with SI/PSF values 96.746 and 83.167, respectively. Structure-activity relationship (SAR) was discussed the effect of substituents insertion on the derivatives activities. Quinazolinone derivatives and related compounds are promising compounds in the mosquito control programs and further studies are recommended to develop more effective derivatives and reveal their mode of action.

Synthesis, larvicidal efficiency and molecular docking studies of novel annulated pyrano[2,3-c]pyrazoles against Culex pipiens L. and Musca domestica L. larvae.

A number of novel annulated pyrazolopyranopyrimidines were prepared via reaction of iminoether of the corresponding 6-amino-5-cyano-pyrano[2,3-c]pyrazole derivative 1 with different nitrogen nucleophiles. The structure of the synthesized compounds was deduced based on IR, MS, 1H NMR and 13C NMR spectroscopic data. The larvicidal potency of the synthesized compounds against the lab and field strains of Culex pipiens and Musca domestica larvae was evaluated and the structure-activity relationship (SAR) was discussed. The assay revealed that the tested pyranopyrazole derivatives exhibited good larvicidal bio-efficacy whereas iminoether 4 exhibited the highest efficiency, for lab more than field strains of both species. Also, M. domestica larvae were more sensitive to tested compounds than C. pipiens. The field strain showed low resistance ratios to all compounds with only about 2 folds. The inhibitory effects of synthesized molecules on nAChRs were evaluated by molecular docking. Moreover, the cytotoxicity of the newly synthesized compounds against normal human fibroblasts (WI-38) was investigated. The cytotoxic assay showed that derivatives 4 and 5 were not harmful to normal fibroblasts.

Synthesis, molecular modelling and evaluation of larvicidal efficacy of annulated Benzo[h]chromenes against Culex pipiens L. Larvae.

A new series of substituted benzo[h]chromene, benzochromenopyrimidine, and benzochromenotriazolopyrimidine derivatives were synthesized via chemical transformations of iminonitrile, ethoxymethylene amino, and cyanomethylene functionalities. The chemical structures of the synthesized compounds were assured by spectroscopic data and elemental analysis. The larvicidal efficacy of these compounds against Culex pipiens L. larvae was investigated, revealing potent insecticidal activity, particularly for compounds 6, 10, and 16, exceeding that of the standard insecticide chlorpyrifos. The mode of action of these compounds was explored through molecular docking studies, indicating their potential as acetylcholine esterase (AChE) inhibitors and nicotinic acetylcholine receptors (nAChR) blockers. The structure-activity relationship analysis highlighted the influence of substituents and fused heterocyclic rings on larvicidal potency. These findings suggest that the synthesized compounds hold promise as potential candidates for developing novel and effective mosquito control agents.

Synthesis of new oxadiazol-phthalazinone derivatives with anti-proliferative activity; molecular docking, pro-apoptotic, and enzyme inhibition profile.

Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.