4z2i › Citations

Creation of Customized Bioactivity within a 14-Membered Macrolide Scaffold: Design, Synthesis, and Biological Evaluation Using a Family-18 Chitinase.

Sugawara A, Maita N, Gouda H, Yamamoto T, Hirose T, Kimura S, Saito Y, Nakano H, Kasai T, Nakano H, Shiomi K, Hirono S, Watanabe T, Taniguchi H, Omura S, Sunazuka T
J Med Chem 58 4984-97 (2015)
Related entries: 4z2g, 4z2h, 4z2j, 4z2k, 4z2l

Cited: 3 times
EuropePMC logo PMID: 26030312

Abstract

Argifin, a 17-membered pentapeptide, inhibits chitinase. As argifin has properties that render it unsuitable as a drug development candidate, we devised a mechanism to create the structural component of argifin that bestows the chitinase inhibition and introduce it into a 14-membered macrolide scaffold. Here we describe (1) the designed macrolide, which exhibits ∼200-fold more potent chitinase inhibition than argifin, (2) the binding modes of the macrolide with Serratia marcescens chitinase B, and (3) the computed analysis explaining the reason for derivatives displaying increased inhibition compared to argifin, the macrolide aglycone displaying inhibition in a nanomolar range. This promises a class of chitinase inhibitors with novel skeletons, providing innovative insight for drug design and the use of macrolides as adaptable, flexible templates for use in drug discovery research and development.

Articles - 4z2i mentioned but not cited (1)

  1. Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies. de Oliveira Viana J, Silva E Souza E, Sbaraini N, Vainstein MH, Gomes JNS, de Moura RO, Barbosa EG. Sci Rep 13 7320 (2023)


Reviews citing this publication (1)

  1. The chemistry and biology of guanidine natural products. Berlinck RGS, Bertonha AF, Takaki M, Rodriguez JPG. Nat Prod Rep 34 1264-1301 (2017)

Articles citing this publication (1)

  1. ForceGen 3D structure and conformer generation: from small lead-like molecules to macrocyclic drugs. Cleves AE, Jain AN. J Comput Aided Mol Des 31 419-439 (2017)


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