title: (+)-Ascosalitoxin and vermelhotin, a calmodulin inhibitor, from an endophytic fungus isolated from Hintonia latiflora.
abstract: Chemical investigation of the endophytic MEXU 26343, isolated from the medicinal plant Hintonia latiflora, yielded the known polyketide vermelhotin (1) and a new salicylic aldehyde derivative, namely, 9S,11R-(+)-ascosalitoxin (2). The structure and absolute configuration of the new compound were established through extensive NMR spectroscopy and molecular modeling calculations at the DFT B3LYP/DGDZVP level, which included the comparison between theoretical and experimental optical rotation values. In addition, chemical transformations of 2 yielded suitable derivatives for NOESY and (1)H-(1)H NMR coupling constant analyses, which reinforce the stereochemical assignment. The potential affinity of 1 and 2 with (Ca(2+))(4)-hCaM in solution was measured using the fluorescent biosensor hCaM M124C-mBBr. The results showed that 1 bound to the protein with a dissociation constant (K(d)) of 0.25 ± 0.04 μM, close to that of chlorpromazine (K(d) = 0.64 ± 0.03 μM), a classical CaM inhibitor. The stoichiometry ratio of 1 to (Ca(2+))(4)-hCaM was 1:4, similar to other well-known CaM ligands.
authors.affiliation: Facultad de Química, Universidad Nacional Autónoma de México, México DF 04510, Mexico.
authors.forename: Martha
authors.initials: M
authors.lastname: Leyte-Lugo
authors.forename: Martín
authors.initials: M
authors.lastname: González-Andrade
authors.forename: María del Carmen
authors.initials: Mdel C
authors.lastname: González
authors.forename: Anthony E
authors.initials: AE
authors.lastname: Glenn
authors.forename: Carlos M
authors.initials: CM
authors.lastname: Cerda-García-Rojas
authors.forename: Rachel
authors.initials: R
authors.lastname: Mata
mesh_terms: D002147:Calmodulin / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D060026:Endophytes / Q000737:chemistry*; D008800:Mexico; D008968:Molecular Conformation; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D018515:Plant Leaves / Q000382:microbiology; D010946:Plants, Medicinal / Q000382:microbiology*; D011759:Pyrrolidines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D012459:Salicylates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: C577383:9S,11R-(+)-ascosalitoxin; D002147:Calmodulin; D011759:Pyrrolidines; D012459:Salicylates; C534203:vermelhotin