02240nas a2200205   4500008004100000022001400041245015900055210006900214260000800283300001400291490000700305520147500312100001601787700001801803700001901821700001901840700003001859700002601889856011901915       2023                        eng d  a1477-052000aTotal synthesis, structure elucidation and expanded bioactivity of icosalide A: effect of lipophilicity and ester to amide substitution on its bioactivity0 aTotal synthesis structure elucidation and expanded bioactivity o  cJUL  a5725-57310 v213 a<p>
	The first total synthesis of icosalide A, an antibacterial depsipeptide that is unique in that it contains two lipophilic beta-hydroxy acids, has been achieved by following Fmoc solid-phase peptide synthesis in combination with solution-phase synthesis. The ambiguity in the absolute stereochemistry of icosalide A has been resolved by synthesizing the reported structures and other relevant diastereomers of icosalides and comparing their NMR data. NMR-based structure elucidation of icosalide A revealed a well-folded structure with cross-strand hydrogen bonds similar to the anti-parallel beta-sheet conformation in peptides and displayed a synergistic juxtaposition of the aliphatic sidechains. 12 analogues of icosalide A were synthesized by varying the constituent lipophilic beta-hydroxy acid residues, and their biological activities against Bacillus thuringiensis and Paenibacillus dendritiformis were explored. Most of these icosalide analogues showed an MIC of 12.5 &amp; mu;g mL(-1) against both bacteria. Swarming inhibition by icosalides was least in B. thuringiensis (8.3%) compared to that in P. dendritiformis (33%). Furthermore, this is the first report of icosalides showing assured inhibitory action (MIC between 2 and 10 &amp; mu;g mL(-1)) against the active stage of Mycobacterium tuberculosis and cancer cell lines such as HeLa and ThP1. This study could help optimize icosalides for anti-TB, antibacterial, and anti-cancer activities.</p>
1 aDangi, Abha1 aPande, Bharat1 aAgrawal, Sonia1 aSarkar, Dhiman1 aVamkudoth, Koteswara, Rao1 aMarelli, Udaya, Kiran  uhttps://library.ncl.res.in/content/total-synthesis-structure-elucidation-and-expanded-bioactivity-icosalide-effect