Ferhat Can Özkaya

Induction of new metabolites from the endophytic fungus Bionectria sp. through bacterial co-culture

A new alkaloid, 1,2-dihydrophenopyrrozin (1), along with five known compounds (2-6) was isolated from an axenic culture of the endophytic fungus, Bionectria sp., obtained from seeds of the tropical plant Raphia taedigera. Co-cultivation of this fungus either with Bacillus subtilis or with Streptomyces lividans resulted in the production of two new o-aminobenzoic acid derivatives, bionectriamines A and B (7 and 8) as well as of two additional known compounds (9 and 10). None of the latter compounds (7-10) were detected in axenic cultures of the fungus or of the bacteria indicating activation of silent biogenetic gene clusters through co-cultivation with bacteria. The structures of the new compounds were unambiguously determined based on detailed NMR and MS spectroscopic analysis and by comparison with the literature. The crystal structure of agathic acid (6) is reported here for the first time. Penicolinate A (4) exhibited potent cytotoxic activity against the human ovarian cancer cell line A2780 with an IC50 value of 4.1μM.

Lactones from the Sponge-Derived Fungus Talaromyces rugulosus

The marine-derived fungus Talaromyces rugulosus isolated from the Mediterranean sponge Axinella cannabina and cultured on solid rice medium yielded seventeen lactone derivatives including five butenolides (1–5), seven (3S)-resorcylide derivatives (6–12), two butenolide-resorcylide dimers (13 and 14), and three dihydroisocoumarins (15–17). Among them, fourteen compounds (1–3, 6–16) are new natural products. The structures of the isolated compounds were elucidated by 1D and 2D NMR (Nuclear Magnetic Resonance) spectroscopy as well as by ESI-HRMS (ElectroSpray Ionization-High Resolution Mass Spectrometry). TDDFT-ECD (Time-Dependent Density Functional Theory-Electronic Circular Dichroism) calculations were performed to determine the absolute configurations of chiral compounds. The butenolide-resorcylide dimers talarodilactones A and B (13 and 14) exhibited potent cytotoxicity against the L5178Y murine lymphoma cell line with IC50 values of 3.9 and 1.3 µM, respectively.

Isolation and X-ray structure analysis of citreohybridonol from marine-derived Penicillium atrovenetum

Abstract The anti-neuroinflammatory meroterpenoid citreohybridonol was isolated for the first time from a sponge-derived fungus Penicillium atrovenetum. In this study, in addition to isolation and structure featuring, its unambiguous absolute configuration was determined exclusively by single crystal X-ray diffraction. The C-17-keto tautomer was clearly observed in X-ray analysis. The substance crystallises in the monoclinic space group P21 with a = 10.7496(5) Å, b = 14.3286(7) Å, c = 17.4909(8) Å, β = 103.235(2)°, V = 2622.5(2) Å3, Z = 2, Dcalcd = 1.280 g/cm3. The chirality of the asymmetric carbon atoms was as follows: C3 (S), C5 (R), C6 (S), C8 (S), C9 (R), C10 (R), C13 (R), C14 (R).

Tanzawaic acid derivatives from freshwater sediment-derived fungus Penicillium sp.

Chemical investigation of a freshwater sediment-derived fungus, Penicillium sp. (S1a1), led to the isolation of three new tanzawaic acid derivatives, including penitanzchroman (1), tanzawaic acids Y (2) and Z (3), along with six known tanzawaic acid analogues (4-9), three known isochromans (10-12) and two known benzoquinones (13 and 14). The structures of the new compounds were established based on high-resolution mass spectrometry, and detailed analysis of one- and two-dimensional NMR spectroscopy. The relative configuration of the new compounds was assigned on the basis of NMR spectroscopic data including ROESY spectra. The absolute configuration was determined based on the specific optical rotation, in addition to biogenetic considerations in comparison with related co-isolated known metabolites. Penitanzchroman (1) constitutes a hitherto unprecedented skeleton, formed of tanzawaic acid A (5) and (3S)-6-hydroxy-8-methoxy-3,5-dimethylisochroman (10) linked by a CC bond. Moreover, all compounds were evaluated for their antibacterial and cytotoxic activities.