New cytotoxic chalcone derivatives from Astragalus ponticus Pall.

Astragalus ponticus Pall. species was investigated for its antiproliferative effects on HeLa cells. Two new chalcones (B5 and B8) along with eight known compounds (B1, B2, B3, B6, B7, B10, B14 and B15) were isolated by following bioactivity guided isolation methods. In addition, from non-active fraction, three cycloartane glycosides (B11, B12 and B13) were isolated. Molecular structures of these isolated compounds were revealed by using spectroscopic methods like MS, 1D and 2D NMR and a single crystal X-ray diffraction analysis. New compounds B5 and B8 showed the highest antiproliferative activities against HeLa cells (IC50 values of 36.6 and 20.6 µM, respectively) while the rest showed high and low activities. Non-endemic species attract relatively low attention from the scientific community but this study demonstrates that valuable new compounds, which might be used as ingredients in medicinal preparations, can be obtained from these materials.

Microwave assisted synthesis, experimental and theoretical characterization and antibacterial activity screening of novel azomethine compounds containing thiophene and aminophenol functionality.

Eight new azomethine compounds (3a-3h) containing thiophene and aminophenol functionality were synthesized in excellent yields by using conventional heating and microwave assisted synthesis methods. The structures of newly synthesized compounds were characterized by spectroscopic techniques such as UV-Vis, FTIR, 1H and 13C NMR and elemental analysis. UV-Vis and 1H NMR results show that all compounds prefer the phenol-imine tautomer form in solvent media. The chemical structure of 3a, 3b and 3g was also confirmed by single crystal X-ray diffraction method. The molecular conformations of 3a, 3b and 3g are stabilized by an N+-H⋯O- type intramolecular hydrogen bond in zwitterionic form in the crystalline solid state. The optimized molecular structures, 1H and 13C NMR chemical shift values, UV-Vis spectroscopic parameters, HOMO-LUMO energies, Mulliken (MPA) and natural (NBO) atomic charges, Natural bond orbitals (NBO), molecular electrostatic potential (MEP) maps and solvent accessible surfaces (SASs) for 3a-3h were calculated by using DFT/B3LYP/6-311G(2d,p) approach. The theoretical spectroscopic features obtained by DFT calculations show a very good agreement with the experimental data. In addition, the synthesized compounds (3a-3h) were screened for their antibacterial activities against Bacillus cereus (NRRL-B3711), Bacillus subtilis (NRRL-B4378), Escherichia coli (NRRL B-3008), Staphylococcus aureus (ATCC-6538) and Salmonella typhimurium (ATCC-13311). The results show that investigated compounds have either moderately active, slightly active or inactive among the tested microorganisms. 3a exhibited the stronger antibacterial activity against all test bacteria than other compounds. It also has been observed that compounds with relatively low HOMO-LUMO energy gaps exhibit better antibacterial effects.

Design, Synthesis, Anti-Proliferative, Anti-microbial, Anti-Angiogenic Activity and In Silico Analysis of Novel Hydrazone Derivatives.

BACKGROUND: Cancer is the second leading cause of death globally. Hydrazone and hydrazone derivatives have high activity, and for this reason, these compound are greatly used by researchers to synthesize new anti-cancer drug. The aim of this research work is to synthesize novel anticancer agents. METHODS: New hydrazone derivatives were synthesized via a reaction between 3-formylphenyl methyl carbonate and benzhydrazide, 4-methylbenzoic hydrazide, 4-tert-butylbenzoic hydrazide, 4-nitrobenzoic hydrazide and 3- methoxybenzoic hydrazide, and were successfully characterized using elemental analysis, 1H-NMR, 13C-NMR, FT-IR and LC-MS techniques. The synthesized compounds were evaluated for their antimicrobial (some grampositive and -negative bacteria, filamentous fungi and yeasts), anti-proliferative (T47D and HCC1428-breast cancer cells) and anti-angiogenic (HUVEC-endothelial cells) activities. The anti-proliferative activities of the hydrazone compounds R1-R5 were studied on these cell lines by MTT assay. The anti-angiogenic potential of the compounds was determined by the endothelial tube formation assay. To identify structural features related to the anti-proliferative activity of these compounds, 2D-QSAR was performed. RESULT: The results indicated that compound R3 exhibited strong anti-angiogenic and anti-proliferative activity on breast cancer cell lines and healthy cell lines. Also, this compound; possessing a tertiary butyl moiety on the hydrazine, exhibited the highest inhibitory effect against all tested microorganisms; in particular, it inhibited Candida albicans at a lower concentration than ketoconazole. Among the investigated compounds, those bearing methyl, tertiary butyl (compound R2, R3) and methoxy (compound R5) moiety were found to be more successful anticandidal derivatives than standard antifungal antibiotics. The QSAR analysis suggested that the tumor specificity of the hydrazone correlated with their molecular weight, lipophilicity, molar refractivity, water solubility, DipolHybrid:(MOPAC) and ExchangeEnergy:(MOPAC). Absorption, Distribution, Metabolism and Elimination (ADME) analysis of the hydrazone compounds showed that they have favorable pharmacokinetic and drug-likeness properties. The ADME results clarify that R3 is the best compound in terms of pharmacokinetic properties. In contrast to other compounds; target prediction analysis of the compound R3 showed inhibitory activity on estrogen-related receptor alpha transcription factor (ESRRA). The target prediction analysis was supported by molinspiration bioactivity score. CONCLUSION: The R3 compound is considered to be an important candidate for future studies with its suitability for the Lipinski's rule of five for drug-likeness, and effective in vitro and in silico results.

Synthesis and Characterization of Two New Thiophene Acetyl Salicylic Acid Esters and their ortho- and para-effect on Anticancer Activity.

OBJECTIVE: The present study aimed to explore the cytotoxic effect of ortho- and para-positional isomers of thiophene acetyl salicylic acid esters against cancer and normal cell lines. METHOD: Two new thiophene-2-acetic acid esters (2-((2-(thiophen-2-yl)acetyl)thio)benzoic acid and 4-((2-(thiophen-2- yl)acetyl)thio)benzoic acid) were synthesized and characterized by Elemental analysis, Fourier transform infrared spectroscopy, 1H-nuclear magnetic resonance (NMR), 13C-NMR and High-resolution mass spectroscopy. The compounds were tested for their in vitro cytotoxic activity against A549 and Caco2 tumor cell lines and CCD- 19Lu and CCD 841 CoN normal cell lines using the 3-(4,5-dimethylthiazol-2-yl)-2,4,diphenyltetrazolium bromide assay. 2-((2-(thiophene-2-yl)acetyl)thio)benzoic acid showed a higher activity with (IC50 = 239.88µM/mL) compared with a reference drug nearly as active as cyclophosphamide (IC50 = 257.11 µM/mL) on Caco2 cell line. Apoptosis was observed by flow cytometric analysis on Caco2 cells. RESULT: Thus, positional isomerism is critical for the pharmacological properties of thiophene acetyl salicylic acid esters against colon cancer cell line compared with nonsmall cell lung cancer cell line. The ortho-isomer induced cell death and was much more potent than the para-isomer.