Structurally diverse secondary metabolites from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001 and their biological evaluation.

Five new compounds, including a cytotoxic dimeric isocoumarin, bipenicilisorin (1), a merosesquiterpenoid, yaminterritrem C (2), a citrinin dimer, penicitrinone F (3), a alkaloid, terremide D (4), and a δ-valerolacton, (E)-4-(propen-1-yl)-5,6-dihydro-2H-pyran-2-one (5), along with ten known compounds (6-15) were isolated from a deep-sea-derived fungus Penicillium chrysogenum SCSIO 41001. Their structures and absolute configurations were elucidated by NMR spectra, MS, CD, optical rotation, X-ray crystallography, and compared with literature data. Biological evaluation results revealed that 1 exhibited significant cytotoxic activities against K562, A549, and Huh-7 cell lines with IC50 values of 6.78, 6.94, and 2.59µM, respectively. Compound 3 exhibited moderate inhibitory activity against EV71 with IC50 value of 14.50µM. In addition, 13 and 14 showed specific COX-2 inhibitory activities with IC50 values of 1.09 and 1.97µM, respectively.

A new citrinin dimer isolated from Aspergillus terreus strain ZDF21.

Dicitrinin E (1), a new citrinin dimer, together with the known metabolites, dicitrinin A (2), citrinin (3), and fumitremorgin C (4), were isolated from the broth culture of Aspergillus terreus strain ZDF21. The structure of dicitrinin E (1) was elucidated through detailed analysis of 1D and 2D NMR experiments, CD and mass spectra The cytotoxicity of 1 was tested against larvae of Artemia salina.

Citrinin produces acute adverse changes in renal function and ultrastructure in pentobarbital-anesthetized dogs without concomitant reductions in [potassium]plasma.

Citrinin's nephrotoxicity was examined in pentobarbital-anesthetized dogs under conditions that minimized or avoided significant changes in a number of its actions that could indirectly and adversely affect renal function and ultrastructure, such as, (i) major acute reductions in blood pressure and renal blood flow and, (ii) emesis and diarrhea that could lead to dehydration and electrolyte imbalances, especially hypokalemia. Slow intravenous injection of 20 mumol citrinin/kg to pentobarbital-anesthetized dogs did not induce any alterations in renal tissue ultrastructure or in any of the 23 whole blood, plasma or renal function parameters that were monitored over a 6-h post-citrinin period. On the other hand, 80 mumol citrinin/kg produced significant increases in the hematocrit and in the renal excretion rates of protein and glucose; modest reductions were noted in CIN, RBF and excretion rate of inorganic phosphorus. In addition, 80 mumol citrinin/kg induced ultrastructural lesions in the cells of the S2 proximal tubular segment, the thick ascending limb, the distal convoluted tubule and the collecting ducts. The glomeruli, S1 and S3 cells of the proximal tubule and the thin descending and ascending limbs of Henle's loop were unaffected by both citrinin doses. The location and nature of the adverse ultrastructural lesions were most likely the result of the direct actions of citrinin (or a citrinin metabolite) since the effects of citrinin that could lead to indirect adverse renal effects were totally avoided or greatly minimized.