Identification of a Novel Series of Potent Organosilicon Mosquito Repellents

Abstract

Mosquito control by personal protection is one of the most efficient ways of curtailing deadly diseases such as malaria and dengue with the potential to save millions of lives per year. DEET (N,N-diethyl-3-methyl benzamide) is currently considered as the gold standard for mosquito repellents, being used for the past several decades. Control by DEET, however, is being threatened by emerging resistance among mosquitoes. To address this concern and also to improve protection times, we synthesized a novel series of 25 silicon-containing acyl piperidines using acid−amine coupling protocol and tested their activity against Aedes aegypti in mosquito-repellent assays. Several compounds from this series appear to possess good mosquito-repellent properties. Most notably, at 0.5 mg/cm 2 concentrations, the mean protection time for NDS100100 was 756 min, which was higher than that of DEET (616 min). The details of design, synthesis, and biological evaluation are discussed herein.

Novel Sophoridine Derivatives as Potential Larvicidal Agents against Aedes albopictus: Synthesis, Biological Evaluation, Acetylcholinesterase Inhibition, and Morphological Study

“…Data for SOP-1: 1 H NMR (500 MHz, CDCl 3 ) δ 9.64 (s, 1H), 3.63 (dd, J = 12.7, 5.6 Hz, 1H), 3.28 (td, J = 7.9, 4.0 Hz, 1H), 3.13-3.05 (m, 1H), 2.90-2.84 (m, 1H), 2.78 (dt, J = 11.8, 6.8 Hz, 1H), 2.37 (ddd, J = 15.9, 8.9, 3.5 Hz, 2H), 2.31-2.24 (m, 2H), 2.22 (dd, J = 11.1, 8.0 Hz, 1H), 2.12-2.02 (m, 1H), 1.84 (tdd, J = 13.3, 9.6, 5.9 Hz, 4H), 1.71 (qt, J = 12.4, 3.7 Hz, 1H), 1.60 (ddd, J = 13.4, 8.4, 3.5 Hz, 1H), 1.50 (qd, J = 11.0, 5.2 Hz, 4H), 1.05 (qd, J = 12.9, 4.2 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 187.…”

“…Data for SOP-2: 1 H NMR (500 MHz, CDCl 3 ) δ 10.90 (s, 1H), 8.20 (s, 1H), 3.52 (dd, J = 11.6, 3.5 Hz, 1H), 3.01-2.91 (m, 4H), 2.83 (dd, J = 10.9, 4.8 Hz, 1H), 2.52 (d, J = 11.3 Hz, 1H), 2.40 (dd, J = 17.2, 6.3 Hz, 1H), 2.31-2.19 (m, 2H), 2.16 (t, J = 11.5 Hz, 1H), 2.11-2.05 (m, 1H), 1.96-1.68 (m, 6H), 1.53-1.43 (m, 2H), 1.33 (d, J = 13.0 Hz, 1H), 1.09 (qd, J = 12.9, 4.1 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 149.…”

“…Data for SOP-2a: The compound was obtained in 80% yield as a white solid. 1 H NMR (500 MHz, CDCl 3 ) δ 8.60 (s, 1H), 8.09 (dd, J = 8.3, 1.2 Hz, 2H), 7.61-7.54 (m, 1H), 7.49-7.43 (m, 2H), 3.61 (dd, J = 12.2, 4.5 Hz, 1H), 3.06 (d, J = 11.6 Hz, 1H), 3.01-2.85 (m, 3H), 2.71 (dd, J = 11.2, 5.4 Hz, 1H), 2.65-2.59 (m, 1H), 2.52-2.43 (m, 2H), 2.37 (t, J = 11.9 Hz, 1H), 2.22 (dtt, J = 15.7, 7.4, 4.2 Hz, 1H), 1.98-1.92 (m, 1H), 1.91-1.82 (m, 2H), 1.79 (ddd, J = 13.7, 6.7, 3.8 Hz, 2H), 1.72 (dd, J = 12.8, 3.7 Hz, 1H), 1.66 (ddd, J = 16.8, 7.9, 3.5 Hz, 2H), 1.50 (dd, J = 12.6, 3.2 Hz, 1H), 1.34 (d, J = 12.6 Hz, 1H), 1.10 (qd, J = 12.7, 4.1 Hz, 1H). 13 C NMR (125 MHz, CDCl 3 ) δ 164.…”

“…Mosquitoes such as Aedes albopictus, Culex quinquefasciatus, and Anopheles gambiae act as vectors that transmit pathogens and cause parasitic and viral infectious diseases (e.g., malaria, dengue, yellow fever, Japanese encephalitis, Chikungunya, West Nile virus, Insects 2023, 14, 399 2 of 19 lymphatic filariasis, and Zika viruses), posing an ongoing threat all over the world. Tropical and subtropical regions are particularly vulnerable because the warm and humid climate creates ideal conditions for mosquito breeding [1][2][3][4][5]. For example, 120 million individuals have lymphatic filariasis transmitted by Culex spiculosus, and about 80% of them reside in tropical nations including Bangladesh, India, Indonesia, Malaysia, Nigeria, and the Philippines [6].…”

New 3-Aminopropylsilatrane Derivatives: Synthesis, Structure, Properties, and Biological Activity

“…For instance, sila-isosteres exhibit better stability, lipophilicity, bioavailability, efficiency, and safety compared with their analogs. Generally, the strategy of bio-sila-isosterism has promising outcomes, and Si-containing structures can become highly effective agents against severe diseases, such as hypertension, diabetes mellitus, HIV, and cancer [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 ].…”