Silva Viviane Barros, Travassos Daniele Lima, Nepel Angelita, Barison Andersson, Costa Emmanoel Vilaça, Scotti Luciana, Scotti Marcus Tulius, Mendonça-Junior Francisco Jaime Bezerra, La Corte Dos Santos Roseli, de Holanda Cavalcanti Sócrates Cabral
Medicinal Chemistry Laboratory, Pharmacy Department, Federal University of Sergipe, São Cristóvão, Brazil.
Nuclear Magnetic Resonance Laboratory, Chemistry Department, Federal University of Paraná, Curitiba, Brazil.
J Arthropod Borne Dis. 2017 May 27;11(2):315-330. eCollection 2017 Jun.
Thymol and carvacrol have previously demonstrated larvicidal activity against (Diptera: Culicidae). In view of this fact, it was of our interest to obtain synthetic derivatives and evaluate their larvicidal activity on larvae.
Structural modifications were performed on thymol and carvacrol in an effort to understand the functional groups necessary for modulating their activities and to lead possibly to more effective larvae control agents. The derivatives were further subjected to SAR and computational studies (molecular modeling and chemometric tools (CPCA and PCA)) to extract structural information regarding their larvicidal properties. Field collected and Rockefeller populations of were used.
Carvacrol and thymol exhibited LC of 51 and 58ppm for field collected larvae, respectively. Carvacrol derivatives exhibited LC ranging from 39 to 169ppm, while thymol derivatives exhibited LC ranging from 18 to 465ppm. Substitution of the acidic proton of carvacrol by esters, ethers, and acetic acid resulted in either maintenance or reduction of potency.
Thymol derivatives were, to a certain extent, more efficient larvicides against than carvacrol derivatives, particularly to Rockefeller larvae. The chemometrics tools applied in this study showed that the independent variables indicate a mixed profile. Nevertheless, hydrophobic interactions increased the larvicidal activity.
百里香酚和香芹酚先前已证明对致倦库蚊（双翅目：蚊科）具有杀幼虫活性。鉴于这一事实，我们有兴趣获得合成衍生物并评估它们对致倦库蚊幼虫的杀幼虫活性。
对百里香酚和香芹酚进行结构修饰，以了解调节其活性所需的官能团，并可能开发出更有效的幼虫控制剂。对这些衍生物进一步进行构效关系（SAR）和计算研究（分子建模和化学计量学工具（CPCA和PCA）），以提取有关其杀幼虫特性的结构信息。使用野外采集的致倦库蚊种群和洛克菲勒致倦库蚊种群。
对于野外采集的幼虫，香芹酚和百里香酚的LC50分别为51ppm和58ppm。香芹酚衍生物的LC50范围为39至169ppm，而百里香酚衍生物的LC50范围为18至465ppm。香芹酚的酸性质子被酯、醚和乙酸取代后，活性要么维持不变，要么降低。
在一定程度上，百里香酚衍生物作为致倦库蚊的杀幼虫剂比香芹酚衍生物更有效，尤其是对洛克菲勒致倦库蚊幼虫。本研究中应用的化学计量学工具表明，自变量呈现出混合特征。然而，疏水相互作用增加了杀幼虫活性。
