Natural products and their derivatives continue to be wellsprings of nascent therapeutic potential. However, many laboratories have limited resources for biological evaluation, leaving their previously isolated or synthesized compounds largely or completely untested. To address this issue, the Canvass library of natural products was assembled, in collaboration with academic and industry researchers, for quantitative high-throughput screening (qHTS) across a diverse set of cell-based and biochemical assays. Characterization of the library in terms of physicochemical properties, structural diversity, and similarity to compounds in publicly available libraries indicates that the Canvass library contains many structural elements in common with approved drugs. The assay data generated were analyzed using a variety of quality control metrics, and the resultant assay profiles were explored using statistical methods, such as clustering and compound promiscuity analyses. Individual compounds were then sorted by structural class and activity profiles. Differential behavior based on these classifications, as well as noteworthy activities, are outlined herein. One such highlight is the activity of (−)-2(S)-cathafoline, which was found to stabilize calcium levels in the endoplasmic reticulum. The workflow described here illustrates a pilot effort to broadly survey the biological potential of natural products by utilizing the power of automation and high-throughput screening.

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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.

Two thiophenes; 5-(3-buten-1-ynyl)-2,2'-bithiophene (2) and α-tertthienyl (9), two alkaloids; echinopsine (10) and echinorine (11), three flavonoids; genkwanin (5), apigenin (6), and rutin (7), two triterpenoids; lupeol acetate (1) and lupeol linoleate (4), together with 2,6,10-trimethyldodeca-2,6,10-triene (4) and β-sitosterol glucoside (8) were isolated from the aerial parts of Echinops albicaulis. Antioxidant, antimicrobial and antiprotozoal activities were evaluated. E. albicaulis aqueous methanolic extract (50, 10, and 1 mg/mL) showed significant antioxidant activity comparable to the potent antioxidant, N-acetyl cysteine, moreover, the aqueous methanolic extract (1 mg/mL) significantly reduced intracellular reactive oxygen species in active cell cultures of human peripheral blood mononuclear cells under oxidative stress more than the reference antioxidant N-acetyl cysteine. None of the isolated compounds showed antimicrobial or antiprotozoal activities at concentration up to 20 μg/mL.