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Fungi usually contain gene clusters that are silent or cryptic under normal laboratory culture conditions. These cryptic genes could be expressed for a wide variety of bioactive compounds. One of the recent approaches to induce production of such cryptic fungal metabolites is to use histone deacetylases (HDACs) inhibitors. In the present study, the cultures of the marine-derived fungus Penicillium brevicompactum treated with nicotinamide and sodium butyrate were found to produce a lot of phenolic compounds. Nicotinamide treatment resulted in the isolation and identification of nine compounds 1–9. Sodium butyrate also enhanced the productivity of anthranilic acid (10) and ergosterol peroxide (11). The antioxidant as well as the antiproliferative activities of each metabolite were determined. Syringic acid (4), sinapic acid (5), and acetosyringone (6) exhibited potent in vitro free radical scavenging, (IC50 20 to 30 µg/mL) and antiproliferative activities (IC50 1.14 to 1.71 µM) against HepG2 cancer cell line. Furthermore, a pharmacophore model of the active compounds was generated to build up a structure-activity relationship.

Bioassay-guided fractionation of the leaves of Eugenia rigida yielded three stilbenes, (Z)-3,4,3',5'-tetramethoxystilbene (1), (E)-3,4,3',5'-tetramethoxystilbene (2), and (E)-3,5,4'-trimethoxystilbene (3). Their structures were determined using 1D- and 2D-NMR spectroscopy and HRESIMS. The sterically hindered Z-stereoisomer 1, a new natural product, was prepared by time-dependent photoisomerization of the E-isomer (2) under UV irradiation at λ254 nm, while 2,3,5,7-tetramethoxyphenanthrene (5) was identified at λ365 nm by UHPLC/APCI-MS and NMR spectroscopy. Compounds 1-3 were tested against a panel of luciferase reporter gene assays that assess the activity of many cancer-related signaling pathways, and the Z-isomer (1) was found to be more potent than the E-isomer (2) in inhibiting the activation of Stat3, Smad3/4, myc, Ets, Notch, and Wnt signaling, with IC50 values between 40 and 80 μM. However, both compounds showed similar inhibition against Ap-1 and NF-κB signaling. In addition, 1 demonstrated cytotoxic activity toward human leukemia cells, solid tumor cells of epidermal, breast, and cervical carcinomas, and skin melanoma, with IC50 values between 3.6 and 4.3 μM, while 2 was weakly active against leukemia, cervical carcinoma, and skin melanoma cells. Interestingly, 2 showed antioxidant activity by inhibition of ROS generation to 50% at 33.3 μM in PMA-induced HL-60 cells, while 1 was inactive at 100 μM (vs Trolox 1.4 μM).

Two new flavonoids, rac-6-formyl-5,7-dihydroxyflavanone (1) and 2',6'-dihydroxy-4'-methoxy-3'-methylchalcone (2), together with five known derivatives, rac-8-formyl-5,7-dihydroxyflavanone (3), 4',6'-dihydroxy-2'-methoxy-3'-methyldihydrochalcone (4), rac-7-hydroxy-5-methoxy-6-methylflavanone (5), 3'-formyl-2',4',6'-trihydroxy-5'-methyldihydrochalcone (6), and 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7), were isolated from the leaves of Eugenia rigida. The individual (S)- and (R)-enantiomers of 1 and 3, together with the corresponding formylated flavones 8 (6-formyl-5,7-dihydroxyflavone) and 9 (8-formyl-5,7-dihydroxyflavone), as well as 2',4',6'-trihydroxychalcone (10), 3'-formyl-2',4',6'-trihydroxychalcone (11), and the corresponding 3'-formyl-2',4',6'-trihydroxydihydrochalcone (7) and 2',4',6'-trihydroxydihydrochalcone (12), were synthesized. The structures of the isolated and synthetic compounds were established via NMR, HRESIMS, and electronic circular dichroism data. In addition, the structures of 3, 5, and 8 were confirmed by single-crystal X-ray diffraction crystallography. The isolated and synthetic flavonoids were evaluated for their antimicrobial and cytotoxic activities against a panel of microorganisms and solid tumor cell lines.

Bioassay-guided fractionation and chemical investigation of Colvillea racemosa stems led to identification of two new α, β-dihydroxydihydrochalcones, colveol A (1) and colveol B (2) along with fifteen known compounds. The structures were elucidated via interpretation of spectroscopic data. The absolute configurations of the dihydrochalcones 1 and 2 were assigned by a combination of chemical modification and electronic circular dichroism data. The isolated compounds were evaluated for their inhibition activity toward recombinant human monoamine oxidases (rhMAO-A and -B). Compound 1 demonstrated preferential inhibition against hMAO-A isoenzyme (IC 0.62μM, SI 0.02) while S-naringenin (13) and isoliquiritigein (15) demonstrated preferential hMAO-B inhibition (IC 0.27 and 0.51μM, SI 31.77 and 44.69, respectively). Fisetin (11) showed inhibition against hMAO-A with IC value of 4.62μM and no inhibitory activity toward hMAO-B up to 100μM. Molecular docking studies for the most active compounds were conducted to demonstrate the putative binding modes. It suggested that 1 interacts with Gln215, Ala111, Phe352, and Phe208 amino acid residues which have a role in the orientation and stabilization of the inhibitor binding to hMAO-A, while S-naringenin (13) occupies both entrance and substrate cavities and interacts with Tyr326, a critical residue in inhibitor recognition in hMAO-B.

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BACKGROUND Mosquitoes remain one of the most significant threats to the health of humans throughout the world. This study was designed to evaluate the biting deterrent effects of a series of ester analogs of undecanoic acid (C:11:0) and dodecanoic acid (C:12:0) against Aedes aegypti (L), (Diptera: Culicidae), the yellow fever mosquito, using Klun and Debboun (K&D) and Ali and Khan (A&K) bioassay systems. RESULTS In the K&D bioassays, C:11:0 esters methyl undecanoate, propyl undecanoate, butyl undecanoate, and pentyl undecanoate, and the C:12:0 esters methyl dodecanoate, ethyl dodecanoate, propyl dodecanoate, octyl dodecanoate, and dodecyl dodecanoate were most active. All of these esters were as effective as N,N‐diethyl‐m‐toluamide (DEET) and as effective as the parent acids undecanoic acid and dodecanoic acid with biting deterrence index values ranging from 0.80 to 0.99. In the in vitro A&K bioassay undecanoic acid with a minimum effective dose (MED) of 3.125 μg cm−2 was the most active compound and showed higher activity than DEET (MED of 25 μg cm−2). The most active synthetic analog was butyl undecanoate with a MED of 12.5 μg cm−2. The next most active analogs are the methyl ester analogs methyl undecanoate and methyl dodecanoate, both with MED values of 25 μg cm−2. CONCLUSION Fatty acid synthetic esters and structural analogs are a promising source of new mosquito repelling compounds and should be investigated further. Published 2020. This article is a U.S. Government work and is in the public domain in the USA.