Metal ions play an important role in biological processes and in metal homeostasis. Metal imbalance is the leading cause for many neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, and multiple sclerosis. 8-Hydroxyquinoline (8HQ) is a small planar molecule with a lipophilic effect and a metal chelating ability. As a result, 8HQ and its derivatives hold medicinal properties such as antineurodegenerative, anticancer, antioxidant, antimicrobial, anti-inflammatory, and antidiabetic activities. Herein, diverse bioactivities of 8HQ and newly synthesized 8HQ-based compounds are discussed together with their mechanisms of actions and structure–activity relationships.

Alkaloid molecules can act, depending on a type of amine functionality present in alkalods, as either hydrogenacceptor or hydrogen-donor for hydrogen bonding that is critically important for the interaction (binding) between targets (enzymes, proteins and receptors) and drugs (ligands). Because of this unique property, alkaloid scaffolds are therefore present in several drugs and lead compounds. This review highlights alkaloid scaffolds in drugs, particularly those recently approved in 2012; it also covers the scaffolds in leads and drug candidates which are in clinical trials and preclinical pipeline. The review focuses on three therapeutic areas including treatments of cancer, tuberculosis, and tobacco cessation. Alkaloid scaffolds in drugs and leads are inspired by those of naturally occurring alkaloids, and these scaffolds include pyridine, piperidine, quinoline, quinolinone, quinazoline, isoquinoline, indole, indolinone, isoindole, isoxazole, imidazole, indazole, thiazole, pyrazole, oxazolidinone, oxadiazole, and benzazepine. In addition to medicinal chemistry aspects, natural products possessing an individual alkaloid scaffold, as well as the mechanism of action of drugs and leads, are also discussed in this review.

Spilanthes acmella Murr. (Compositae) has been used as a traditional medicine for toothache, rheumatism and fever. Its extracts had been shown to exhibit vasorelaxant and antioxidant activities. Herein, its antimicrobial, antioxidant and cytotoxic activities were evaluated. Agar dilution method assays against 27 strains of microorganisms were performed. Results showed that fractions from the chloroform and methanol extracts inhibited the growth of many tested organisms, e.g. Corynebacterium diphtheriae NCTC 10356 with minimum inhibitory concentration (MIC) of 64-256 μg/mL and Bacillus subtilis ATCC 6633 with MIC of 128-256 μg/mL. The tested fractions all exhibited antioxidant properties in both DPPH and SOD assays. Potent radical scavenging activity was observed in the DPPH assay. No cytotoxic effects of the extracts against KB and HuCCA-1 cell lines were evident. Bioassay-guided isolation resulted in a diverse group of bioactive compounds such as phenolics [vanillic acid (2), trans-ferulic acid (5) and trans-isoferulic acid (6)], coumarin (scopoletin, 4) and triterpenoids like 3-acetylaleuritolic acid (1), β-sitostenone (3), stigmasterol and stigmasteryl-3-O-β-D-glucopyranosides, in addition to a mixture of stigmasteryl-and β-sitosteryl-3-O-β-D-glucopyranosides. The compounds 1–6 represent bioactive metabolites of S. acmella Murr. that were never previously reported. Our findings demonstrate for the first time the potential benefits of this medicinal plant as a rich source of high therapeutic value compounds for medicines, cosmetics, supplements and as a health food.

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Hydnophytum formicarum Jack. (Rubiaceae) is a medicinal plant whose tubers possesses cardiovascular, anti-inflammatory and antiparasitic effects and have been used for the treatment of hepatitis, rheumatism and diarrhea. Herein we report the isolation of its active constituents and the testing of their antimicrobial activity against 27 strains of microorganisms using an agar dilution method and of their antioxidative activity using the DPPH and SOD assays. The results show that the crude hexane, dichloromethane, ethyl acetate and methanol extracts exert such activities. Particularly, the crude ethyl acetate extract exhibits antigrowth activity against many Gram-positive and Gram-negative bacteria with MIC 256 μg/mL. Shewanella putrefaciens ATCC 8671 is completely inhibited at a lower MIC (128 μg/mL). Interestingly, Corynebacterium diphtheriae NCTC 10356 is inhibited by all the tested extracts. Significantly, the ethyl acetate extract is also the most potent antioxidant, showing 83.31% radical scavenging activity with IC50 8.40 μg/mL in the DPPH assay. The other extracts display weak to moderate antioxidative activities, ranging from 28.60-56.80% radical scavenging. The SOD assay shows that methanol extract exhibits the highest activity (74.19% inhibition of superoxide radical). The dichloromethane and ethyl acetate extracts display comparable SOD activity. The promising bioactivities of the crude ethyl acetate extract guided the first isolation of bioactive flavonoid and phenolic compounds: isoliquiritigenin (2), protocatechualdehyde (3), butin (4) and butein (5) from this species. Their structures have been fully established by 1D and 2D NMR. In addition, stigmasterol was isolated from the crude hexane and dichloromethane extracts. The antimicrobial and cytotoxic activities of compounds 3-5 were evaluated. The tested compounds were inactive against HuCCA-1 and KB cell lines, showing ED50> 10 μg/mL. Protocatechualdehyde (3) completely inhibits the growth of Plesiomonas shigelloides with MIC ≤60 μg/mL. As a result, we propose that Hydnophytum formicarum Jack. can serve as a new source enriched with potent antioxidative and antimicrobial agents.