177329-69-0Relevant articles and documents
Norepinephrine alkaloids as antiplasmodial agents: Synthesis of syncarpamide and insight into the structure-activity relationships of its analogues as antiplasmodial agents
Aratikatla, Eswar K.,Valkute, Tushar R.,Puri, Sunil K.,Srivastava, Kumkum,Bhattacharya, Asish K.
, p. 1089 - 1105 (2017/08/03)
Syncarpamide 1, a norepinephrine alkaloid isolated from the leaves of Zanthoxylum syncarpum (Rutaceae) exhibited promising antiplasmodial activities against Plasmodium falciparum with reported IC50 values of 2.04 μM (D6 clone), 3.06 μM (W2 clone) and observed by us 3.90 μM (3D7 clone) and 2.56 μM (K1 clone). In continuation of our work on naturally occurring antimalarial compounds, synthesis of syncarpamide 1 and its enantiomer, (R)-2 using Sharpless asymmetric dihydroxylation as a key step has been accomplished. In order to study structure-activity-relationship (SAR) in detail, a library of 55 compounds (3–57), which are analogues/homologues of syncarpamide 1 were synthesized by varying the substituents on the aromatic ring, by changing the stereocentre at the C-7 and/or by varying the acid groups in the ester and/or amide side chain based on the natural product lead molecule and further assayed in vitro against 3D7 and K1 strains of P. falciparum to evaluate their antiplasmodial activities. In order to study the effect of position of functional groups on antiplasmodial activity profile, a regioisomer (S)-58 of syncarpamide 1 was synthesized however, it turned out to be inactive against both the strains. Two compounds, (S)-41 and its enantiomer, (R)-42 having 3,4,5-trimethoxy cinnamoyl groups as side chains showed better antiplasmodial activity with IC50 values of 3.16, 2.28 μM (3D7) and 1.78, 2.07 μM (K1), respectively than the natural product, syncarpamide 1. Three compounds (S)-13, (S)-17, (S)-21 exhibited antiplasmodial activities with IC50 values of 6.39, 6.82, 6.41 μM against 3D7 strain, 4.27, 7.26, 2.71 μM against K1 strain and with CC50 values of 147.72, 153.0, >200 μM respectively. The in vitro antiplasmodial activity data of synthesized library suggests that the electron density and possibility of resonance in both the ester and amide side chains increases the antiplasmodial activity as compared to the parent natural product 1. The natural product syncarpamide 1 and four analogues/homologues out of the synthesized library of 55, (S)-41, (R)-42, (S)-55 and (S)-57 were assayed in vivo assay against chloroquine-resistant P. yoelii (N-67) strain of Plasmodium. However, none of the five molecules, 1, (S)-41, (R)-42, (S)-55 and (S)-57 exhibited any promising in vivo antimalarial activity against P. yoelii (N-67) strain. Compounds 4, 6, 7 and 11 showed high cytotoxicities with CC50 values of 5.87, 5.08, 6.44 and 14.04 μM, respectively. Compound 6 was found to be the most cytotoxic as compared to the standard drug, podophyllotoxin whereas compounds 4 and 7 showed comparable cytotoxicities to podophyllotoxin.
Synthesis and biological evaluation of 2-Indolyloxazolines as a new class of tubulin polymerization inhibitors. Discovery of A-289099 as an orally active antitumor agent
Li, Qun,Woods, Keith W.,Claiborne, Akiyo,Gwaltney, Ii, Stephen L.,Barr, Kenneth J.,Liu, Gang,Gehrke, Laura,Credo,Hui, Yu Hua,Lee, Jang,Warner, Robert B.,Kovar, Peter,Nukkala, Michael A.,Zielinski, Nicolette A.,Tahir, Stephen K.,Fitzgerald, Michael,Kim, Ki H.,Marsh, Kennan,Frost, David,Ng, Shi-Chung,Rosenberg, Saul,Sham, Hing L.
, p. 465 - 469 (2007/10/03)
A series of indole containing oxazolines has been discovered as a result of structural modifications of the lead compound A-105972. The compounds exert their anticancer activity through inhibition of tubulin polymerization by binding at the colchicine site. A-289099 was identified as an orally active antimitotic agent active against various cancer cell lines including those that express the MDR phenotype. The anticancer activity, pharmacokinetics, and an efficient and enantioselective synthesis of A-289099 are described.
Enantioselective synthesis of natural combretastatin
Ramacciotti, Alessio,Fiaschi, Rita,Napolitano, Elio
, p. 1101 - 1104 (2007/10/03)
In a process which appears to be general for the enantioselective synthesis of oxysubstituted 1,2-diarylethanols, a 4-methoxy-3-silyloxyphenyllithium, obtained by bromine-lithium exchange from the corresponding aryl bromide and t-butyllithium, added selectively at the b-carbon of (S)-2,3,4-trimethoxyphenyloxirane, elaborated from the corresponding styrene via Sharpless asymmetric dihydroxylation, to afford an adduct from which natural (-)-combretastatin was obtained by desilylation.
