199679-35-1Relevant articles and documents
Design, Synthesis, and Anticancer Activity of Cinnamoylated Barbituric Acid Derivatives
Liu, Yue,Li, Peng-Xiao,Mu, Wen-Wen,Sun, Ya-Lei,Liu, Ren-Min,Yang, Jie,Liu, Guo-Yun
, (2022/01/13)
This work deals with the design and synthesis of 18 barbituric acid derivatives bearing 1,3-dimethylbarbituric acid and cinnamic acid scaffolds to find potent anticancer agents. The target molecules were obtained through Knoevenagel condensation and acylation reaction. The cytotoxicity was assessed by the MTT assay. Flowcytometry was performed to determine the cell cycle arrest, apoptosis, ROS levels and the loss of MMP. The ratios of GSH/GSSG and the MDA levels were determined by using UV spectrophotometry. The results revealed that introducing substitutions (CF3, OCF3, F) on the meta- of the benzyl ring of barbituric acid derivatives led to a considerable increase in the antiproliferative activities compared with that of corresponding ortho- and para-substituted barbituric acid derivatives. Mechanism investigation implied that the 1c could increase the ROS and MDA level, decrease the ratio of GSH/GSSG and MMP, and lead to cell cycle arrest. Further research is needed for structural optimization to enhance hydrophilicity, thereby improve the biological activity of these compounds.
Larvicidal activity and in silico studies of cinnamic acid derivatives against Aedes aegypti (Diptera: Culicidae)
Bezerra Fran?a, Saraliny,Carine Barros de Lima, Luana,Rychard da Silva Cunha, Cristhyan,Santos Anuncia??o, Daniela,Ferreira da Silva-Júnior, Edeildo,Ester de Sá Barreto Barros, Maria,José da Paz Lima, Dimas
, (2021/07/07)
Cinnamic acid derivatives (CAD's) represent a great alternative in the search for insecticides against Aedes aegypti mosquitoes since they have antimicrobial and insecticide properties. Ae. aegypti is responsible for transmitting Dengue, Chikungunya, and Zika viruses, among other arboviruses associated with morbimortality, especially in developing countries. In view of this, in vitro analyses of n-substituted cinnamic acids and esters were performed upon 4th instar larvae (L4) of Ae. aegypti, as well as, molecular docking studies to propose a potential biological target towards this mosquitoes species. The larvicide assays proved that n-substituted ethyl cinnamates showed a more pronounced activity than their corresponding acids, in which p-chlorocinnamate (3j) presented a LC50 value of 8.3 μg/mL. Thusly, external morphologic alterations (rigid and elongated body, curved bowel, and translucent or darkened anal papillae) of mosquitoes’ group exposed to compound 3j, were observed by microscopy. In addition, an analytical method was developed for the quantification of the most promising analog by using high-performance liquid chromatography with UV detection (HPLC-UV). Molecular docking studies suggested that the larvicide action is associated with inhibition of acetylcholinesterase (AChE) enzyme. Therefore, expanding the larvicidal study with the cinnamic acid derivatives against the vector Ae. aegypti is important for finding search for more effective larvicides and with lower toxicity, since they have already shown good larvicidal properties against Ae. aegypti.
Development of sulfonamides incorporating phenylacrylamido functionalities as carbonic anhydrase isoforms I, II, IX and XII inhibitors
Angapelly, Srinivas,Ramya, P.V. Sri,Angeli, Andrea,Del Prete, Sonia,Capasso, Clemente,Arifuddin, Mohammed,Supuran, Claudiu T.
, p. 5726 - 5732 (2017/10/09)
A series of novel sulfonamides incorporating phenylacrylamido functionalities were synthesized and investigated for the inhibition of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The physiologically and pharmacologically relevant human (h) isoforms hCA I and II (cytosolic isozymes), as well as the transmembrane tumor-associated hCA IX and XII were included in the study. These compounds showed low nanomolar or sub-nanomolar inhibition constants against hCA II (KIs in the range of 0.50–50.5 nM), hCA IX (KIs of 1.8–228.5 nM), and hCA XII (KIs of 3.5–96.2 nM) being less effective as inhibitors of the off target isoform hCA I. A detailed structure–activity relationship study demonstrates that the nature and position of substituents present on the aromatic part of the scaffold strongly influence the inhibition of CA isoforms. As hCA II, IX and XII are involved in pathologies such as glaucoma and hypoxic, and metastatic tumors, compounds of the type reported in this work may be useful preclinical candidates.
