title: Syntheses of a library of molecules on the marine natural product ianthelliformisamines platform and their biological evaluation.
abstract: Ianthelliformisamines A-C are a novel class of bromotyrosine-derived antibacterial agents isolated recently from the marine sponge Suberea ianthelliformis. We have synthesized ianthelliformisamines A-C straightforwardly by the condensation of (E)-3-(3,5-dibromo-4-methoxyphenyl)acrylic acid and the corresponding Boc-protected polyamine followed by Boc-deprotection with TFA. Further, using this reaction protocol, a library of their analogues (39 analogues) has been synthesized by employing 3-phenylacrylic acid derivatives and Boc-protected polyamine chains through various combinations of these two fragments differing in phenyl ring substitution, double bond geometry or chain length of the central spacer of the polyamine chain (shown in red color). All the synthesized compounds (ianthelliformisamines A-C and their analogues) were screened for antibacterial activity against both Gram-negative (Escherichia coli) and Gram-positive (Staphylococcus aureus) strains. All synthetic analogues of ianthelliformisamine A showed bacterial growth inhibition against both strains (Escherichia coli and Staphylococcus aureus), having MIC values in the range of 117.8-0.10 μM, while none of the synthetic analogues of ianthelliformisamine C as well as the parent compound showed any detectable antibacterial activity. Interestingly, some of the synthetic analogues of ianthelliformisamines A and B exerted a bactericidal effect against both E. coli and S. aureus strains, decreasing viable bacterial count by 99% at concentrations as low as 2 × MIC.
authors.affiliation: Department of Chemistry, Indian Institute of Technology Hyderabad, Ordnance Factory Estate, Yeddumailaram-502205, India. faiz@iith.ac.in.
authors.forename: Faiz Ahmed
authors.initials: FA
authors.lastname: Khan
authors.forename: Saeed
authors.initials: S
authors.lastname: Ahmad
authors.forename: Naveena
authors.initials: N
authors.lastname: Kodipelli
authors.forename: Gururaj
authors.initials: G
authors.lastname: Shivange
authors.forename: Roy
authors.initials: R
authors.lastname: Anindya
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D059001:Aquatic Organisms / Q000737:chemistry*; D001688:Biological Products / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011161:Porifera / Q000737:chemistry*; D054852:Small Molecule Libraries; D013211:Staphylococcus aureus / Q000187:drug effects; D014443:Tyrosine / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000470:Alkaloids; D000900:Anti-Bacterial Agents; D001688:Biological Products; D054852:Small Molecule Libraries; D014443:Tyrosine