Isolation and synthesis of falcitidin, a novel myxobacterial-derived acyltetrapeptide with activity against the malaria target falcipain-2.

A 384-well microtitre plate fluorescence cleavage assay was developed to identify inhibitors of the cysteine protease falcipain-2, an important antimalarial drug target. Bioassay-guided isolation of a MeOH extract from a myxobacterium Chitinophaga sp. Y23 isolated from soil collected in Singapore, led to the identification of a new acyltetrapeptide, falcitidin (1), which displayed an IC50 value of 6 μM against falcipain-2.

Sundaicumones A and B, polyprenylated acylphloroglucinol derivatives from Calophyllumsundaicum with weak activity against the glucocorticoid receptor.

Bioassay-directed fractionation using a glucocorticoid receptor assay led to the isolation of two new, weakly active polyprenylated acylphloroglucinol derivatives, sundaicumones A (1) and B (2), from the leaves of Calophyllum sundaicum collected in Singapore. The structures of 1 and 2, which were established by spectroscopic methods, contain a 3-substituted hexanoic acid unit not previously reported in other polyprenylated acylphloroglucinols.

NMR spectral assignments of three aspidofractinine alkaloids, kopsine, fruticosine and fruticosamine.

1D and 2D NMR techniques were used to assign fully the spectra of three aspidofractinine alkaloids, kopsine (1), fruticosamine (2) and fruticosine (3), isolated from a cultivated specimen of the plant Kopsia fruticosa (Apocynaceae). The assignment of the NMR data for 1, 2 and 3 will help in the future assignments of related alkaloids.

Inhibition of the human chemokine receptor CCR5 by variecolin and variecolol and isolation of four new variecolin analogues, emericolins A-D, from Emericella aurantiobrunnea.

An extract from the fungus Emericella aurantiobrunnea was found to compete with macrophage inflammatory protein (MIP)-1alpha for binding to human CCR5 in a scintillation proximity assay (SPA). Bioassay-guided fractionation led to the isolation of variecolin (1) and variecolol (2), which had IC50 values of 9 and 32 microM, respectively. An X-ray crystal structure of variecolin (1) was obtained for the first time.