1,2,3-Triazolyl-tetrahydropyrimidine Conjugates as Potential Sterol Carrier Protein-2 Inhibitors: Larvicidal Activity against the Malaria Vector <i>Anopheles arabiensis</i> and In Silico Molecular Docking Study
Katharigatta N. Venugopala,
Pottathil Shinu,
Christophe Tratrat,
Pran Kishore Deb,
Raquel M. Gleiser,
Sandeep Chandrashekharappa,
Deepak Chopra,
Mahesh Attimarad,
Anroop B. Nair,
Nagaraja Sreeharsha,
Fawzi M. Mahomoodally,
Michelyne Haroun,
Mahmoud Kandeel,
Syed Mohammed Basheeruddin Asdaq,
Viresh Mohanlall,
Nizar A. Al-Shar’i,
Mohamed A. Morsy
Affiliations
Katharigatta N. Venugopala
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Pottathil Shinu
Department of Biomedical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Christophe Tratrat
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Pran Kishore Deb
Department of Pharmaceutical Sciences, Faculty of Pharmacy, Philadelphia University, Amman 19392, Jordan
Raquel M. Gleiser
CREAN-IMBIV (UNC-CONICET), Av. Valparaiso s.n. and FCEFyN, Universidad Nacional de Cordoba, AV. Sarsfield 299, Cordoba 5000, Argentina
Sandeep Chandrashekharappa
Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER-R) Raebareli, Lucknow, UP 226002, India
Deepak Chopra
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal By-Pass Road, Bhauri, Bhopal, MP 462066, India
Mahesh Attimarad
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Anroop B. Nair
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Nagaraja Sreeharsha
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Fawzi M. Mahomoodally
Department of Health Sciences, Faculty of Medicine and Health Science, University of Mauritius, Réduit 80837, Mauritius
Michelyne Haroun
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Mahmoud Kandeel
Department of Biomedical Sciences, College of Veterinary Medicine, King Faisal University, Al-Ahsa 31982, Saudi Arabia
Syed Mohammed Basheeruddin Asdaq
Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Dariyah, Riyadh 13713, Saudi Arabia
Viresh Mohanlall
Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa
Nizar A. Al-Shar’i
Department of Medicinal Chemistry and Pharmacognosy, Faculty of Pharmacy, Jordan University of Science and Technology, Irbid 22110, Jordan
Mohamed A. Morsy
Department of Pharmaceutical Sciences, College of Clinical Pharmacy, King Faisal University, Al-Ahsa 31982, Saudi Arabia
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.
