Synthesis and Cytotoxicity of Thieno[2,3-b]Pyridine Derivatives Toward Sensitive and Multidrug-Resistant Leukemia Cells.

A new series of substituted ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a-e were prepared by utilizing ethyl 2-chloro-7-cyclopropyl-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylate (1) and replacing of the 2-chlorine with anions obtained from phenol (2a), salicylaldehyde derivatives 2b-d or thiophenol (2e), leading to the respective ethyl 7-cyclopropyl-2-(2-aryloxo)-3-nitro-4-oxo-4,7-dihydrothieno[2,3-b]pyridine-5-carboxylates 3a-e. The new compounds were evaluated for their in vitro cytotoxicity towards sensitive CCRF-CEM and multidrug-resistant CEM/ADR5000 leukemia cells. The screening revealed that compounds 3a, 3b, and 3e inhibited the growth of both cell lines. Compound 3b, with a phenol moiety, exhibited the highest growth inhibitory activity against CEM/ADR5000 and CCRF-CEM cells with IC50 values 4.486 ± 0.286 and 2.580 ± 0.550 µM, respectively. Collectively, the presented results demonstrate that the synthesized thieno[2,3-b]pyridines warrant further exploration for potential use as anti-cancer agents.

Ficus plants: State of the art from a phytochemical, pharmacological, and toxicological perspective.

Ficus genus is typically tropical plants and is among the earliest fruit trees cultivated by humans. Ficus carica L. is the common fig, Ficus benjamina L. is the weeping fig, and Ficus pumila L. is the creeping fig. These species are commonly used in traditional medicine for a wide range of diseases and contain rich secondary metabolites that have shown diverse applications. This comprehensive review describes for Ficus genus the phytochemical compounds, traditional uses and contemporary pharmacological activities such as antioxidant, cytotoxic, antimicrobial, anti-inflammatory, antidiabetic, antiulcer, and anticonvulsant. An extended survey of the current literature (Science Direct, Scopus, PubMed) has been carried out as part of the current work. The trends in the phytochemistry, pharmacological mechanisms and activities of Ficus genus are overviewed in this manuscript: antimicrobial, antidiabetic, anti-inflammatory and analgesic activity, antiseizure and anti-Parkinson's diseases, cytotoxic and antioxidant. Health-promoting effects, recent human clinical studies, safety and adverse effects of Ficus plants also are covered. The medical potential and long-term pharmacotherapeutic use of the genus Ficus along with no serious reported adverse events, suggests that it can be considered as being safe.

Evaluation of Triazole and Isoxazole Derivatives as Potential Anti-infective Agents.

A series of isoxazole and triazole derivatives, with interesting bioactive scaffolds, were examined for their in vitro antibacterial, antifungal, and antiprotozoal activities. These compounds exhibited antitrypanosomal activity comparable to difluoromethylornithine (DMFO), a drug used in the treatment of human African trypanosomiasis. Isoxazole analogues 1, 3 and 4, and triazole derivatives 16, 17, 28, 37, 40 and 42 showed the highest antitrypanosomal activity with IC50 values of 17.89, 1.82, 10.38, 10.26, 11.77, 9.29, 3.93, 2.11, and 0.93 µM, respectively. Compounds 40 and 42 showed the most potent activity against Leishmania donovani amastigotes with IC50 values of 18.28 and 10.54 µM, respectively. Compound 42 showed the most potent activity against Leishmania donovani macrophage internalized amastigotes with an IC50 value of 8.32 µM. Conjugate triazoles 40-43 displayed potential antimalarial activity against chloroquine-resistant W2 and chloroquine sensitive D6 Plasmodium falciparum strains (IC50 value range from 0.58 to 8.36 µM). Compound 37 showed antibacterial activity against Staphylococcus aureus, MRSA and Mycobacterium intracellulare with IC50 values of 15.53, 14.22 and 47.45 µM, respectively. None of the compounds exhibited antifungal activity.

Sulfated phenolic compounds from Limonium caspium: Isolation, structural elucidation, and biological evaluation.

Three new compounds, (2S,3S)-5-methyldihydromyricetin (1), (2S,3S)-5-methyldihydromyricetin-3'-O-sulfate (2) and ß-d-glucopyranoside, 3-methyl, but-3-en-1-yl 4-O-α-l-rhamnopyranosyl (3) have been isolated from the Limonium caspium, together with dihydromyricetin (4), dihydromyricetin-3'-O-sulfate (5), myricetin-3'-O-sulfate (6), 5-methylmyricetin (7), myricetin (8), myricetin-3-O-ß-glucoside (9), as well as phloridzin (10), and tyramine (11). Compounds 5 and 6 were isolated for the first time as acids. This is the first report of all these compounds from this plant. Their structures were established by extensive NMR studies ((1)H NMR, (13)C NMR, DEPT, (1)H-(1)H COSY, HSQC, HMBC) as well as HRESIMS. All isolated compounds were evaluated for their antibacterial, antifungal, antimalarial and antileishmanial activities. Compounds 7, 8 and 9 exhibited good antifungal activity against Candida glabrata with IC50 values of 6.79, 15.37 and 8.53µg/mL, respectively. Compound 8 displayed significant antimalarial activity against resistant and sensitive strains of Plasmodium falciparum with IC50 values of 1.82 and 1.51µg/mL, respectively. Compounds 1, 4, 6, 8 and 9 showed excellent activity against Trypanosoma brucei with IC50 values of 6.93, 9.65, 8.52, 7.67 and 6.31µg/mL, respectively. To date, this is the first report on the phytochemical and biological activity of secondary metabolites from L. caspium.