Resistance development to bioinsecticides in Aedes aegypti (Culicidae: Diptera), the vector of dengue fever in Saudi Arabia

A laboratory strain of Aedes aegypti (L) was subjected repeatedly to larval selection pressure with two bacterial insecticides, spinosad (Saccharopolyspora spinosa) and bacilod (Bacillus thuringiensis israelensis). The results indicated that the mosquito Ae. aegypti acquired low resistance to spinosad and bacilod by about 3.1 and 2.4-fold, respectively, due to selection pressure for fifteen successive generations. The slope values of the selected strains were increased gradually from one generation to the next, indicating moderate homogeneity between individuals in their response to the test bio-insecticide. Moreover, larval selection with current bacterial bioinsecticides prolonged the time required to digest a blood meal. It showed an evident decrease in the reproductive potential of adult mosquitoes surviving selected larvae

Synthesis, Cytotoxic Evaluation, and Structure-Activity Relationship of Substituted Quinazolinones as Cyclin-Dependent Kinase 9 Inhibitors

Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcriptional elongation, through which short-lived antiapoptotic proteins are overexpressed and make cancer cells resistant to apoptosis. Therefore, CDK9 inhibition depletes antiapoptotic proteins, which in turn leads to the reinstatement of apoptosis in cancer cells. Twenty-seven compounds were synthesized, and their CDK9 inhibitory and cytotoxic activities were evaluated. Compounds 7, 9, and 25 were the most potent CDK9 inhibitors, with IC50 values of 0.115, 0.131, and 0.142 μM, respectively. The binding modes of these molecules were studied via molecular docking, which shows that they occupy the adenosine triphosphate binding site of CDK9. Of these three molecules, compound 25 shows good drug-like properties, as it does not violate Lipinski’s rule of five. In addition, this molecule shows promising ligand and lipophilic efficiency values and is an ideal candidate for further optimization