Comparative Analysis of Antioxidant, Anticholinesterase, and Antibacterial Activity of Microbial Chondroitin Sulfate and Commercial Chondroitin Sulfate.

Chondroitin synthesis was performed using the recombinant Escherichia coli(C2987) strain created by transforming the plasmid pETM6-PACF-vgb, which carries the genes responsible for chondroitin synthesis, kfoA, kfoC, kfoF, and the Vitreoscilla hemoglobin gene (vgb). Then, Microbial chondroitin sulfate (MCS)'s antioxidant, anticholinesterase, and antibacterial activity were compared with commercial chondroitin sulfate (CCS). The antioxidant studies revealed that the MCS and CCS samples could be potential targets for scavenging radicals and cupric ion reduction. MCS demonstrated better antioxidant properties in the ABTS assay with the IC50 value of 0.66 mg than CCS. MCS showed 2.5-fold for DPPH and almost 5-fold for ABTS⋅+ (with a value of 3.85 mg/mL) better activity than the CCS. However, the compounds were not active for cholinesterase enzyme inhibitions. In the antibacterial assay, the Minimum inhibitory concentration (MIC) values of MCS against S. aureus, E. aerogenes, E. coli, P. aeruginosa, and K. pneumoniae (0.12, 0.18, 0.12, 0.18, and 0.18 g/mL, respectively) were found to be greater than that of CCS (0.42, 0.48, 0.36, 0.36, and 0.36 g/mL, respectively). This study demonstrates that MCS is a potent pharmacological agent due to its physicochemical properties, and its usability as a therapeutic-preventive agent will shed light on future studies.

Dimethoxyindoles based thiosemicarbazones as multi-target agents; synthesis, crystal interactions, biological activity and molecular modeling.

Alzheimer's disease (AD) is known as one of the most devastating neurodegenerative disease diagnosed for the old-aged people and cholinesterase inhibitors (ChEI) can be used as an effective palliative treatment for AD. A range of novel monomeric and dimeric indole based thiosemicarbazone derivatives 17-28 was synthesized in order to target cholinesterases (ChE). Biological importance of the targeted compounds 17-28 was investigated by employing the acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes along with three different antioxidant property determination assays, namely DPPH free radical scavenging, ABTS cationic radical decolarization, and CUPRAC cupric reducing antioxidant capacity. The compounds 18 and 19 displayed the best inhibitor activity against BChE with IC50 values of 7.42 and 1.95 µM, respectively. The antioxidant potentials were found to be moderate for DPPH and ABTS assays and the compounds 28 and 18 were the most potent candidates for both antioxidant assays. Cupric reducing capacity was the most promising assay and the compounds 25, 26 and 28 provided better inhibition values than all the standards. Further binding mode and affinity studies performed by molecular docking and molecular dynamics simulations. Accordingly, the compound 19 is the most plausible candidate that can compete with galantamine (GNT), a common pharmaceutics targeting both cholinesterase enzymes.

Synthesis and Characterisation of Novel Tricyclic and Tetracyclic Furoindoles: Biological Evaluation as SAHA Enhancer against Neuroblastoma and Breast Cancer Cells.

The dihydropyranoindole structures were previously identified as promising scaffolds for improving the anti-cancer activity of histone deacetylase inhibitors. This work describes the synthesis of related furoindoles and their ability to synergize with suberoylanilide hydroxamic acid (SAHA) against neuroblastoma and breast cancer cells. The nucleophilic substitution of hydroxyindole methyl esters with α-haloketones yielded the corresponding arylether ketones, which were subsequently cyclized to tricyclic and tetracyclic furoindoles. The furoindoles showed promising individual cytotoxic efficiency against breast cancer cells, as well as decent SAHA enhancement against cancer cells in select cases. Interestingly, the best IC50 value was obtained with the non-cyclized intermediate.

Synthesis, Characterization and Biological Evaluation of Novel Dihydropyranoindoles Improving the Anticancer Effects of HDAC Inhibitors.

The dihydropyranoindole scaffold was identified as a promising target for improving the anti-cancer activity of HDAC inhibitors from the preliminary screening of a library of compounds. A suitable methodology has been developed for the preparation of novel dihydropyranoindoles via the Hemetsberger indole synthesis using azido-phenylacrylates, derived from the reaction of corresponding alkynyl-benzaldehydes with methyl azidoacetate, followed by thermal cyclization in high boiling solvents. Anti-cancer activity of all the newly synthesized compounds was evaluated against the SH-SY5Y and Kelly neuroblastoma cells as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Biological studies showed that the tetracyclic systems had significant cytotoxic activity at higher concentration against the neuroblastoma cancer cells. More importantly, these systems, at the lower concentration, considerably enhanced the SAHA toxicity. In addition to that, the toxicity of designated systems on the healthy human cells was found to be significantly less than the cancer cells.

Synthesis, Characterization and Anti-Cancer Activity of Hydrazide Derivatives Incorporating a Quinoline Moiety.

Identification of the novel (E)-N'-((2-chloro-7-methoxyquinolin-3-yl)methylene)-3-(phenylthio)propanehydrazide scaffold 18 has led to the development of a new series of biologically active hydrazide compounds. The parent compound 18 and new quinoline derivatives 19-26 were prepared from the corresponding quinoline hydrazones and substituted carboxylic acids using EDC-mediated peptide coupling reactions. Further modification of the parent compound 18 was achieved by replacement of the quinoline moiety with other aromatic systems. All the newly synthesized compounds were evaluated for their anti-cancer activity against the SH-SY5Y and Kelly neuroblastoma cell lines, as well as the MDA-MB-231 and MCF-7 breast adenocarcinoma cell lines. Analogues 19 and 22 significantly reduced the cell viability of neuroblastoma cancer cells with micromolar potency and significant selectivity over normal cells. The quinoline hydrazide 22 also induced G1 cell cycle arrest, as well as upregulation of the p27(kip1) cell cycle regulating protein.

The synthesis of boronic-imine structured compounds and identification of their anticancer, antimicrobial and antioxidant activities.

Boronic acid compounds with different substituted groups were handled to synthesize various ligands encoded as B1, B2, B3, B4, B5, B6, B7 and B8. B5 and B7 were tested for the cytotoxic activity against the prostate cancer cells and it was found that the cell viability of cancer cells was decreased while most of the healthy cells could still be viable. 5 µM solutions of B5 and B7 decreased the cell viability to 33% and 44% whereas healthy cells were 71% and 95%, respectively, after treatment. Antimicrobial properties were explored against the bacterial and fungal microorganisms with B1, B5 and B7. The inhibition zones were evaluated for all boronic structures, and the growth inhibition zones were determined in a range of 7-13 mm diameter for different microorganism species. Staphylococcus aureus was the common microorganism that three boronic compounds with imine ligands showed the activity. Antioxidant features of B2, B3, B4, B5, B6, B7 and B8 were investigated by different processes such as Beta-carotene bleaching (BCB), 2,2-diphenyl picryl hydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS) and CUPric reducing antioxidant capacity (CUPRAC) methods. Significant antioxidant activity was achieved by the phenyl boronic based ligands and these compounds demonstrated as much activity as standards (α-Toc and BHT). In addition, all structures were applied properly without any decomposition during the experiments. They were rather stable both in aqueous media and solid state.