synthesis and antiviral activity of conformational analogues of leucamide a合成和抗病毒活性构象leucamide的类似物.pdf

Molecules 2012, 17, 14522-14530; doi:10.3390/molecules171214522 OPEN ACCESS molecules ISSN 1420-3049 /journal/molecules Article Synthesis and Antiviral Activity of Conformational Analogues of Leucamide A Wen-Long Wang 1,2, Hai-Jun Chen 2, Wei-Ping Ma 2, Min Gu 2, Min-Zhi Fan 2, Jing-Ya Li 2, Bainian Feng 1,* and Fa-Jun Nan 2,* 1 School of Pharmaceutical Science, Jiangnan University, Wuxi 214122, China; E-Mail: wenlongwang@ 2 Chinese National Center for Drug Screening, Shanghai Institute of Materia Medica, Shanghai Institutes of Biological Sciences, Graduate School of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 201203, China; E-Mails: chj.gy@126.com (H.-J.C.); wpma@ (W.-P.M.); mgu@ (M.G.); mzfan@ (M.-Z.F.); jyli@ (J.-Y.L.) * Authors to whom correspondence should be addressed; E-Mails: fengbainian@ (B.F.); fjnan@ (F.-J.N.); Tel./Fax: +86-21-5080-0954 (F.-J.N.). Received: 1 November 2012; in revised form: 28 November 2012 / Accepted: 30 November 2012 / Published: 7 December 2012 Abstract: In order to study the effect of heterocyclic core conformational state of leucamide A on its anti-influenza virus A activity, five conformational analogues were prepared by replacing the Pro-Leu dipeptide in the molecule with various amino acids. The amino acids used were of 2 to 6 carbons. The results showed that these replacements not only changed the conformational relationship between the 4,2-bisheterocycle tandem pair and the third heterocycle, but also had dramatic effect on its activity