From the stem bark of Acacia nilotica (L) Delile, two new peltogynoids, acanilol A (1) and acanilol B (2) were isolated together with the known triterpene lupenone. The structures of the new compounds were established on the basis of their spectral data, mainly UV, NMR and mass spectrometry. The new compounds were tested as kinase inhibitors against CDK1, GSK3, CK1 and DYRK1A, and acanilol B was identified as a DYRK1A inhibitor, with an IC50 of 19µM.

A series of 3,3-dimethyl-3 Hbenzothieno[3,2- f][1]-benzopyran analogues modified at the pyran 1,2-double bond were synthesized. The corresponding dihydro and (±)-cis-diol derivatives were converted into diacetate and cyclic carbonate upon acylation. The title compounds were characterized by spectroscopic analysis and screened for their antimicrobial activity in vitro.

Benzo[c]phenanthrolines and benzo[c]phenanthrolinones substituted by dialkylaminoalkyl side chains at position N5 and C6, respectively, were synthesised and their biological activity evaluated. They displayed interessant cytotoxicity associated with some DNA interactions. However, the low topoisomerase 1 affinity suggests that other cellular targets are responsible for the antiproliferative activity.

Reaction of 11-aminoacronycine, 10-aminobenzo[a]acronycine, and 10-aminobenzo[b]acronycine with paraformaldehyde gave the corresponding Tröger’s bases 11, 14, and 16, respectively. The cytotoxic activity of those three new compounds was determined against L-1210 leukemia and KB-3-1 solid tumor cell lines, in comparison with their parent compounds, acronycine, benzo[a]acronycine, and benzo[b]acronycine.

The study reports the isolation and structural identification of two new flavonol triglycosides from the methanolic extract of Anthyllis hermanniae, exhibiting the same glycosylation pattern: quercetin 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside]-7-O-α-l-rhamnopyranoside (1) and kaempferol 3-O-[α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside]-7-O-α-l-rhamnopyranoside (2). A conformational study related to the central arabinoside moiety was carried out including the analysis of the contribution of NOE effects and acetylation to the elucidation of the 2-O-linked arabinoside configuration of the anomeric carbon. We also report the total synthesis of a model compound, quercetin 3-O-α-l-rhamnopyranosyl-(1→2)-α-l-arabinopyranoside (3), which verifies the structures of the isolated compounds.

The impact of substitutions at position 10 in the A ring of the cytotoxic benzo[a]acronycine and benzo[b]acronycine series has been explored. 10-Bromobenzo[a] and 10-bromobenzo[b]acronycine were prepared in 12% and 15% yield respectively from commercially available chemicals. Their 1,2-dihydro-1,2-dihydroxy diesters were synthesized. The different derivatives were tested against two cell lines KB-3-1 and L1210. Their cytotoxic activities were found in the same range of magnitude as their non-substituted counterparts. These structure-activity relationships permitted to conclude that the introduction of a substituent at position 10 maintains the activity in both the benzo[a] and [b]acronycine series and open the way to further pharmacomodulations.

The essential oils of Anthospermum emirnense Baker and Anthospermum perrieri Homolle ex Puff , obtained by hydrodistillation in 0.03 and 0.02% yield, respectively, were analyzed by GC/MS. In both cases, the major constituents consisted of sesquiterpene hydrocarbons and oxygenated sesquiterpenes. The two species showed an important qualitative similarity, with 40 compounds common to A. emirnense and A. perrieri , including β ‐elemene, trans‐β ‐caryophyllene, caryophyllene oxide, and τ ‐cadinol, which were major components in both cases. When tested for antimicrobial activity, both essential oils showed similar profiles and exhibited interesting minimal‐inhibitory‐concentration ( MIC ) values towards Bacillus subtilis, Chryseobacterium indologenes, Flavimonas oryzihabitans , and Yersinia enterocolitica.

A new acylated tritrepene, 3β-hexadecanoyloxy-lup-20(29)-en-21-ol (1), along with seven known compounds, lupeol (2), betulinic acid (3), ursonic acid (4), -sitosterol (5), β-stigmasterol (6), 3-O-β-D-glucopyranosyl-β-stigmasterol (7), and palmitic acid (8), were isolated from the leaves of Rauvolfia vomitoria (Apocynaceae). Their structures were established on the basis of spectroscopic analysis and chemical evidence. The new acylated triterpene exhibited interesting antimicrobial activity against Candida albicans (a yeast) with the MIC value 64 μg/mL.

The domino reaction of o-bromobenzamides 1a-m in the presence of K(2)CO(3) and the [PdCl(2)(PPh(3))(2)] catalyst granted a selective access to phenanthridinones 2 or to the new 1-carboxamide phenanthridinones 3 depending on the solvent, DMF or 1,4-dioxane, respectively. Investigations of the reaction parameters provided the first example of a direct correlation between the base dissociation and the solvent polarity on the selectivity observed. Moreover, mechanistic studies (NMR spectroscopy and ESI-MS monitoring) allowed us to characterize Pd(II) palladacycle 4 and biaryl species as common intermediates for these two domino processes. On that basis, C(sp(2))-C(sp(2)) bond formation is envisaged by generation of a Pd(IV) complex after oxidative addition of 1 into Pd(II) palladacycle 4, a rationale that is supported by DFT calculations. A general catalytic cycle is proposed to account for these observations.

Tumor blood vessels are an important emerging target for anti-cancer therapy. The antimitotic agent combretastatin A-4 (CA-4), a cis-stilbene natural product isolated from the South African tree Combretum caffrum Kuntze, is the lead compound of a new class of anti-cancer drugs that target tumor vasculature. CA-4 inhibits tubulin polymerization by interacting at the colchicine binding site on tubulin. This alters the morphology of endothelial cells and causes vascular shutdown and regression of tumor vasculature. Some tubulin-binding vascular-disrupting agents (VDAs) are currently in clinical trials for cancer therapy. As a consequence of the potential favorable applications of these compounds, several analogs projected to induce rapid and selective vascular shutdown in tumors have been synthesized during the last few years. Many of these molecules have already been tested for their effects on tubulin polymerization as well as for their antiproliferative activity and other biological properties, and possible mechanisms of action have been investigated. The aim of the present review is to offer an overview of most recently developed combretastatin derivatives, focusing on biological effects exerted by these compounds. The published data about new analogs are presented and compared, and a detailed investigation of structure-activity relationships is described.

This chapter contains sections titled: Introduction Biomimetic Synthesis of Indolomonoterpene Alkaloids with a Non-rearranged Monoterpene Unit: Aristotelia Alkaloids Biomimetic Synthesis of Secologanin-Derived Indolomonoterpene Alkaloids Biomimetic Synthesis of Secologanin-Derived Quinoline Alkaloids Biomimetic Synthesis of Dimeric Indolomonoterpene Alkaloids Conclusion References

A series of chalcones (1-9) and pyrazoles (10-18) was prepared to investigate their potential activity as Angiotensin I-Converting Enzyme (ACE) inhibitors. Their structures were verified by elemental analysis, UV, IR, MS, H-1 NMR, C-13 NMR, and 2D NMR experiments. Among tested compounds, chalcone 7 exerted the highest activity with an IC50 value of 0.219 mM, while the most potent pyrazole was 15 (IC50 value of 0.213 mM). (C) 2010 Elsevier Ltd. All rights reserved.

AbstractTitle compounds (IV) as well as its [1,8]‐regioisomers display more potent cytotoxicity toward L1210 cells than the unsubstituted parent compounds, associated with strong DNA interaction.

To evaluate the antimicrobial activity of the methanol extract from the stem bark of Drypetes tessmanniana, fractions (DTB1-5) as well as compounds [friedelin (2), 3,7-dioxofriedelane (3), 3,15-dioxofriedelane (4), 3β- O-(E)-3,5-dihydroxycinnamoyl-11-oxo-olean-12-ene (6), and 3β,6α-dihydroxylup-20(29)-ene (7).

Benzo[c][1,7] and [1,8]phenanthroline substituted by dialkylaminoalkyl side chains at position C2 and C1, respectively, were synthesized and their biological activity evaluated. These compounds displayed more potent cytotoxicity toward L1210 cells than the parent unsubstituted compounds, associated with strong DNA interaction. The moderate TopoI inhibitory activity induced by the novel compounds suggests that other cellular targets should be responsible for the antiproliferative activity.

Five new unsaturated iridolactones 3-7 related to natural cytotoxic oxylipins, Tei 9826, and iridolactone 2, were prepared by parallel synthesis from natural aucubin. It was found that perpivaloyl iridoid glucosides 2, 3, and 4 were markedly cytotoxic against both L1210 and KB-3-1 cell lines.

The 8-, 9-, 10-, and 11-halo, hydroxy, and methoxy derivatives of the antimycobacterial 3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran were synthesized by condensation of the diazonium salts of 2-chloroanilines (13–17) with 1,4-benzoquinone (18), reduction of the intermediate phenylbenzoquinones 19–22 to dihydroxybiphenyls, cyclisation to halo-2-hydroxydibenzofurans 24–27, and construction of the pyran ring by thermal rearrangement of the corresponding dimethylpropargyl ethers 35–38. Palladium catalyzed nucleophilic aromatic substitution permitted conversion of the halo to the corresponding hydroxy derivatives which were methylated to methoxy-3,3-dimethyl-3H-benzofuro[3,2-f][1]benzopyran. All compounds substituted on the A ring were found more potent than the reference compound 1 against Mycobacterium bovis BCG and the virulent strain Mycobacterium tuberculosis H37Rv. The effect of the most active derivatives on mycolate synthesis was explored in order to confirm the preliminary hypothesis of an effect on mycobacterial cell wall biosynthesis. The linear 9-methoxy-2,2-dimethyl-2H-benzofuro[2,3-g][1]benzopyran (46) exhibiting a good antimycobacterial activity and devoid of cytotoxicity appeared to be the most promising compound.