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Sixteen diterpenes ( 1 - 16 ), along with 10 previously described compounds, including four flavonoids and six diterpenes, were isolated from the aerial parts of Psiadia punctulata growing in Saudi Arabia. The diterpene structures were elucidated using NMR spectroscopy and mass spectrometry data. Furthermore, a DFT/NMR procedure was used to suggest the relative configuration of several compounds. The labdane-derived skeletons, namely, ent -atisane, ent -beyerene, ent -trachylobane, and ent -kaurene, were identified. The extracts, fractions, and pure compounds were then tested against Staphylococcus aureus , Streptococcus mutans , Treponema denticola , and Lactobacillus plantarum . One diterpenoid, namely, psiadin, showed an additive effect with the antiseptic chlorhexidine, with a fractional inhibitory concentration index of less than 1. Additionally, psiadin showed a prospective inhibition activity for bacterial efflux pumps.

Seven new terpenoids, namely, guaiane ( 1 - 4 ), eudesmane ( 5 ), and bisabolane ( 6 ) sesquiterpenoids and a furanone ( 7 ), were isolated from the aerial parts of Ammoides atlantica , a herbaceous plant growing in Algeria, together with eight known compounds. All metabolites were characterized by their 1D and 2D NMR and HRESIMS data. A combined DFT/NMR method was applied to study the relative configurations of 1 - 4 , 6 , and 7 . All compounds, except 2 , were assayed against MCF-7, A375, A549, HaCaT, and Jurkat cell lines. Compounds 8 , 10 , and 11 induced a dose-dependent reduction in cell viability with different potency on almost all cell lines used. The most active compounds, 8 and 10 , were studied to assess their potential apoptotic effects and cell cycle inhibition.

Nine new limonoids ( 1 - 9 ) were isolated from the stem bark of Guarea guidonia ( 1 - 4 ) and Cedrela odorata ( 5 - 9 ). Their structures were elucidated using 1D and 2D NMR and MS data and chemical methods as three A2,B,D- seco -type limonoids ( 1 - 3 ), a mexicanolide ( 4 ), three nomilin-type ( 5 - 7 ) limonoids, and two limonol derivatives ( 8 and 9 ). A DFT/NMR procedure was used to define the relative configurations of 1 and 3 . A surface plasmon resonance approach was used to screen the Hsp90 binding capability of the limonoids, and the A2,B,D- seco -type limonoid 8-hydro-(8 S* ,9 S *)-dihydroxy-14,15-en-chisomicine A, named chisomicine D ( 1 ), demonstrated the highest affinity. By means of mass spectrometry data, biochemical and cellular assays, and molecular docking, 1 was found as a type of client-selective Hsp90 inhibitor binding to the C-terminus domain of the chaperone.

Ten new (1-10) and six known (11-16) fusicoccane diterpenes were isolated from the roots of Hypoestes forsskaolii. The structural characterization of 1-10 was performed by spectroscopic analysis, including 1D and 2D NMR, ECD, and HRESIMS experiments. From a perspective of obtaining potential Hsp90α inhibitors, the isolates were screened by surface plasmon resonance measurements and their cytotoxic activity was assayed using Jurkat and HeLa cancer cells. Compound 6, 18-hydroxyhypoestenone, was shown to be the most active compound against Hsp90, and its interactions were studied also by biochemical and cellular assays and by molecular docking.

Two new glucopyranosylbianthrones (1 and 2) were isolated from the aerial part of the plant Asphodelus tenuifolius, collected in Southwest Algeria. The 2D structures of 1 and 2 were defined by NMR analysis, HRESIMS data, and comparison with literature data. The comparison of experimental and calculated electronic circular dichroism and NMR data led to characterization of the ( M) and ( P) atropisomeric forms of the glucopyranosylbianthrones, asphodelins (1) and (2), respectively. The in vitro activities of these two metabolites were evaluated in human melanoma A375 cells, and both the compounds inhibited cell proliferation in a concentration-dependent manner, with IC 50 values of 20.6 ± 0.8 and 23.2 ± 1.1 μM, respectively. Considering their biological profile, an inverse virtual screening approach was employed to identify and suggest putative anticancer interacting targets.

Curcumin, or diferuloylmethane, a polyphenolic molecule isolated from the rhizome of Curcuma longa, is reported to modulate multiple molecular targets involved in cancer and inflammatory processes. On the basis of its pan-inhibitory characteristics, here we show that simple chemical modifications of the curcumin scaffold can regulate its biological selectivity. In particular, the curcumin scaffold was modified with three types of substituents at positions C-1, C-8, and/or C-8' [C5 (isopentenyl, 5-8), C10 (geranyl, 9-12), and C15 (farnesyl, 13, 14)] in order to make these molecules more selective than the parent compound toward two specific targets: histone deacetylase (HDAC) and microsomal prostaglandin E2 synthase-1 (mPGES-1). From combined in silico and in vitro analyses, three selective inhibitors by proper substitution at position 8 were revealed. Compound 13 has improved HDAC inhibitory activity and selectivity with respect to the parent compound, while 5 and 9 block the mPGES-1 enzyme. We hypothesize about the covalent interaction of curcumin, 5, and 9 with the mPGES-1 binding site.