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Two novel chemokine receptor CCR-5 inhibitors, Sch 210971 (1) and Sch 210972 (2), were isolated from the fungal fermentation broth of Chaetomium globosum by normal- and reversed-phase HPLC purifications. The structure determination of 1 and 2 was accomplished on the basis of UV, MS, and NMR spectral data analyses including COSY, NOESY, HMQC, and HMBC experiments. The structure and relative configuration of 2 were determined unequivocally by X-ray crystallographic analysis. The major component 2 demonstrated a potent inhibitory activity of IC(50) = 79 nM in the CCR-5 receptor in vitro binding assay.

A novel primase inhibitor, Sch 642305 (1), was isolated from the fermentation broth of the fungal culture Penicillium verrucosum. The structure of 1 was elucidated on the basis of MS and NMR spectroscopic data as a new and unusual bicyclic 10-membered macrolide. The absolute configuration of the asymmetric centers was determined by X-ray crystallographic analysis of the p-bromobenzoate derivative (3). Compound 1 exhibited inhibitory activity against bacterial DNA primase enzyme with an EC(50) of 70 microM.

The novel bromotyrosine derivative verongamine [1] has been isolated from the marine sponge Verongula gigantea. The isolation of verongamine was facilitated by employing histamine-H3 bioassay-guided fractionation. Verongamine is a specific histamine-H3 antagonist at concentrations as low as 1 microgram/ml.