1,2,3-Triazolyl-tetrahydropyrimidine conjugates as potential Sterol Carrier Protein-2 Inhibitors: Larvicidal activity against the Malaria Vector Anopheles arabiensis and In Silico Molecular Docking Study

Alteration of insect growth regulators by the action of inhibitors is becoming an attractive strategy to combat disease-transmitting insects. In the present study, we investigated the larvicidal effect of 1,2,3-triazolyl-pyrimidinone derivatives against the larvae of the mosquito Anopheles arabiensis, a vector of malaria. All compounds demonstrated insecticidal activity against mosquito larvae in a dose-dependent fashion. A preliminary study of the structure–activity relationship indicated that the electron-withdrawing substituent in the para position of the 4-phenyl-pyrimidinone moiety enhanced the molecules’ potency. A docking study of these derivatives revealed favorable binding affinity for the sterol carrier protein-2 receptor, a protein present in the intestine of the mosquito larvae. Being effective insecticides against the malaria-transmitting Anopheles arabiensis, 1,2,3-triazole-based pyrimidinones represent a starting point to develop novel inhibitors of insect growth regulators.Fil: Venugopala, Katharigatta N.. Durban University Of Technology; Sudáfrica. King Faisal University; Arabia SauditaFil: Shinu, Pottathil. King Faisal University; Arabia SauditaFil: Tratrat, Christophe. King Faisal University; Arabia SauditaFil: Deb, Pran Kishore. Philadelphia University Jordan; JordaniaFil: Gleiser, Raquel M.. Universidad Nacional de Córdoba; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (P). Grupo Vinculado Centro de Relevamiento y Evaluación de Recursos Agrícolas y Naturales; ArgentinaFil: Chandrashekharappa, Sandeep. National Institute Of Pharmaceutical Education And Research, Raebareli; IndiaFil: Chopra, Deepak. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Attimarad, Mahesh. King Faisal University; Arabia SauditaFil: Nair, Anroop B.. King Faisal University; Arabia SauditaFil: Sreeharsha, Nagaraja. Vidya Siri College Of Pharmacy; India. King Faisal University; Arabia SauditaFil: Mahomoodally, Fawzi M.. University Of Mauritius; MauricioFil: Haroun, Michelyne. King Faisal University; Arabia SauditaFil: Kandeel, Mahmoud. Faculty Of Veteinary Medicine; Egipto. King Faisal University; Arabia SauditaFil: Asdaq, Syed Mohammed Basheeruddin. Almaarefa University; Arabia SauditaFil: Mohanlall, Viresh. Durban University Of Technology; SudáfricaFil: Al-Shari, Nizar A.. Jordan University Of Science And Technology; JordaniaFil: Morsy, Mohamed A.. King Faisal University; Arabia Saudita. Faculty Of Medicine; Egipt

Larvicidal activities of 2-Aryl-2,3-Dihydroquinazolin -4-ones against malaria vector Anopheles arabiensis, In Silico ADMET prediction and molecular target investigation

Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.Fil: Venugopala, K. N.. Durban University Of Technology; SudáfricaFil: Pushpalatha, R.. Reva University; IndiaFil: Tratat, C.. King Faisal University; Arabia SauditaFil: Gleiser, Raquel M.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Instituto Multidisciplinar de Biología Vegetal (P). Grupo Vinculado Centro de Relevamiento y Evaluación de Recursos Agrícolas y Naturales; ArgentinaFil: Bhandary, S.. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Chopra, D.. Indian Institute Of Science Education And Research Bhopal; IndiaFil: Morsy, M.. King Faisal University; Arabia SauditaFil: Al-Dhubiab, B. E.. King Faisal University; Arabia SauditaFil: Attimarad, M. B.. King Faisal University; Arabia SauditaFil: Nair, A.. King Faisal University; Arabia SauditaFil: Sreeharsha, N.. King Faisal University; Arabia SauditaFil: Venugopala, R.. University Of Kwazulu-natal; SudáfricaFil: Deb, P. K.. Philadelphia University; JordaniaFil: Chandrashekharappa, S.. Institute For Stem Cell Biology And Regenerative Medicine; IndiaFil: Khalil, H.. King Faisal University; Arabia SauditaFil: Alwassil, O.. King Saud Bin Abdulaziz University For Health Sciences; Arabia SauditaFil: Abed, S. N.. Philadelphia University; JordaniaFil: Bataineh, Y. A.. Philadelphia University; JordaniaFil: Palenge, R.. Reva University; IndiaFil: Haroun, M.. King Faisal University; Arabia SauditaFil: Pottathil, S.. King Faisal University; Arabia SauditaFil: Girish, M. B.. Reva University; IndiaFil: Akrawi, S. H.. King Faisal University; Arabia SauditaFil: Mohanlall, V.. Durban University Of Technology; Sudáfric

Two Group A Streptococcal Peptide Pheromones Act through Opposing Rgg Regulators to Control Biofilm Development

Streptococcus pyogenes (Group A Streptococcus, GAS) is an important human commensal that occasionally causes localized infections and less frequently causes severe invasive disease with high mortality rates. How GAS regulates expression of factors used to colonize the host and avoid immune responses remains poorly understood. Intercellular communication is an important means by which bacteria coordinate gene expression to defend against host assaults and competing bacteria, yet no conserved cell-to-cell signaling system has been elucidated in GAS. Encoded within the GAS genome are four rgg-like genes, two of which (rgg2 and rgg3) have no previously described function. We tested the hypothesis that rgg2 or rgg3 rely on extracellular peptides to control target-gene regulation. We found that Rgg2 and Rgg3 together tightly regulate two linked genes encoding new peptide pheromones. Rgg2 activates transcription of and is required for full induction of the pheromone genes, while Rgg3 plays an antagonistic role and represses pheromone expression. The active pheromone signals, termed SHP2 and SHP3, are short and hydrophobic (DI[I/L]IIVGG), and, though highly similar in sequence, their ability to disrupt Rgg3-DNA complexes were observed to be different, indicating that specificity and differential activation of promoters are characteristics of the Rgg2/3 regulatory circuit. SHP-pheromone signaling requires an intact oligopeptide permease (opp) and a metalloprotease (eep), supporting the model that pro-peptides are secreted, processed to the mature form, and subsequently imported to the cytoplasm to interact directly with the Rgg receptors. At least one consequence of pheromone stimulation of the Rgg2/3 pathway is increased biogenesis of biofilms, which counteracts negative regulation of biofilms by RopB (Rgg1). These data provide the first demonstration that Rgg-dependent quorum sensing functions in GAS and substantiate the role that Rggs play as peptide receptors across the Firmicute phylum

Persuasive and pervasive sensing: A new frontier to monitor, track and assist older adults suffering from type-2 diabetes

10.1109/HICSS.2013.618Proceedings of the Annual Hawaii International Conference on System Sciences2636-264