New cyclometalated iridium(III) complexes bearing substituted 2-(1H-benzimidazol-2-yl)quinoline: Synthesis, characterization, electrochemical and anticancer studies.

New iridium(III) compounds (C1-C3) bearing 2-(1H-benzimidazol-2-yl)quinoline ligands with different side groups (benzyl, 2,3,4,5,6-pentamethylbenzyl and 2,3,4,5,6-pentafluorobenzyl) were synthesized and characterized by using spectroscopic analyses. The effects of different side groups of iridium compounds on the photophysical and electrochemical properties have been investigated. The cytotoxicity and apoptosis of the compounds have been evaluated on breast cancer cell lines using various methods including MTT assay, flow cytometry, qRT-PCR, and colony formation. The cytotoxicity of C1, expressed as IC50 values, was found to be 11.76 µM for MDA-MB-231 and 5.35 µM for MCF-7 cells. For C3, the IC50 value was 16.22 µM for MDA-MB-231 and 8.85 µM for MCF-7 cells. In both cell lines, increased levels of Bax and caspase 3, along with downregulation of BCL-2 and positive annexin V staining, were observed, confirming apoptosis. Moreover, the colony-forming abilities in both cell lines decreased after C1 and C3 complex treatment. All these results suggest that the compounds C1 and C3 may have potential in the treatment of breast cancer, though further research is needed to confirm their efficacy.

Evaluation of the effect of injectable platelet-rich fibrin (i-PRF) in wound healing and growth factor release in rats: a split-mouth study.

This experimental study aimed to evaluate the effects of injectable platelet-rich fibrin (i-PRF) on mucosal healing and the release of growth factors in rats. 40 rats were used; i-PRF was administered in the right buccal area while saline was injected in the left. Cytokeratin, FGF, PDGF, TGF, and VEGF expressions were determined with immunohistochemistry. Gene expressions of EGF, TGF-ß, and VEGF were analysed. Epithelialization started on the 3rd day, and connective tissue maturation was more prominent in the i-PRF-applied group. Also, the releases of VEGF, EGF, TGF-ß, PDGF, and FGF were higher in the i-PRF group during the 14 days. Gene expression analysis showed that changes in TGF-ß at 14 days after i-PRF injection and VEGF after 21 days were statistically significant. The results of this study suggested that autologous i-PRF application enhanced the healing of oral mucosal wounds by increasing the release of growth factors for 21 days.

Evaluating Antibiofilm, Cytotoxic and Apoptotic Activities of Scutellaria brevibracteata subsp. brevibracteata Essential Oil.

Essential oils have many important biological properties, including antibacterial and antibiofilm activities. These unique properties make, essential oils good alternatives to synthetic chemical drugs, which have many side effects. In this study, we aimed to determine the chemical composition and biological activity of the essential oil obtained from Scutellaria brevibracteata subsp. brevibracteata. Specifically, its antibiofilm activity against Pseudomonas aeruginosa PAO1 and Staphylococcus aureus ATCC 29213 biofilms using XTT assay. Cytotoxic and apoptotic properties of the essential oil were investigated in human lung cancer cells (A540 and H1299) using MTT assay, Annexin V-FITC and propidium iodide staining and q-PCR. Thirty-two different compounds were identified from the essential oil, of which elemol (20.42 %), γ-eudesmol (20.12 %) and ß-eudesmol (14.85 %) were the main components. The essential oil was more effective against P. aeruginosa PAO1 biofilm (79 %) than S. aureus ATCC 29213 biofilm (27 %). The specific activity of the essential oil against P. aeruginosa biofilm may be related to its high terpene contents. In addition, the essential oil showed high cytotoxic activity towards A549 (IC50 9.09 µg/ml) and H1299 (IC50 55.04 µg/ml) cell lines, inducing apoptosis in these cancer cells. These results demonstrate the antibiofilm and anticancer activities of S. brevibracteata subsp. brevibracteata essential oil.

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.

Design, synthesis and pharmacological evaluation of novel Artemisinin-Thymol.

A molecular hybridization of natural products is a new concept in drug discovery and having critical roles to design new molecules with improved biological properties. Hybrid molecules display higher biological activities when compared to the parent drugs. In the present study, two natural products (thymol and artemisinin (ART)) are used for the synthesis of new hybrid thymol-artemisinin. After characterization, the cytotoxic activity of ART-thymol was tested against different cancer cell lines and non-cancerous human cell line. ART-Thymol show the cytotoxic effect with EC50 values 70,96µM for HepG2, 97,31µM for LnCap, 6,03µM for Caco-2, 77,98µM for HeLa and 62,28µM for HEK293 cells, respectively. Moreover, ART-Thymol was checked for drug-likeness, and the kinase inhibitory activity. ART-Thymol is investigated by using molecular docking. The results of qPCR was indicated CDK2 and P38 were inhibited by ART-Thymol. These results improved that thymol-artemisinin may be new candidates as an anticancer agents.

A Novel 4H-Chromen-4-One Derivative from Marine Streptomyces ovatisporus S4702T as Potential Antibacterial and Anti-Cancer Agent.

BACKGROUND: Marine actinomycetes are among indispensable sources of natural bioactive compounds with unique antimicrobial and anti-cancer activities. OBJECTIVE: Herein, it was aimed to elucidate the bioactive potential of a marine-derived Streptomyces ovatisporus S4702T, isolated previously. METHODS: Streptomyces ovatisporus S4702T was cultured in N-Z Amine broth, and extraction was carried out using different organic solvents. Bioassay-guided purification was followed by chemical characterization using NMR and LC-MS/MS. The compound was then evaluated for its antibacterial, antioxidant and cytotoxic activities. RESULTS: Etyl acetate extracts gave the highest antibacterial activity, and chemical characterization of this extract indicated the formula as C15H29O5N3 and the corresponding possible molecular structure as 4H-chromen-4-one derivative. It was found highly potent against Bacillus subtilis ATCC 6633 (MIC: 0.25 µg ml-1) and Micrococcus luteus ATCC 9341 (MBC: 0.5 µg ml-1). It has no remarkable antioxidant activity, but a higher EC50 value and less cytotoxicity against normal cells. The EC50 values of this chromen derivative were found as 9.68 µg ml-1 for human colon carcinoma, 9.93 µg ml-1 for human prostate adenocarcinoma and 25.5 µg ml-1 for human embryonic kidney cells. CONCLUSION: Overall, the presented 4H-chromen-4-one derivative is a remarkable bioactive compound with potent antibacterial and cytotoxic activity. With its high bioactive potential, it is proposed as a good candidate in medicine.

Assessment of Cytotoxic and Apoptotic Effects of Salvia syriaca L. in Colorectal Adenocarcinoma Cell Line (Caco-2).

This work is aimed to elucidate cytotoxic and apoptotic effects of Salvia syriaca essential oil and its chemical composition by GC-MS. The human colon cancer cells (Caco-2) were treated with different essential oil concentrations for 24 h. Crystal violet test was used to determine cell viability at 630 nm by using an ELISA reader. Apoptotic processes were measured by Annexin V-FITC Apoptosis Assay Kit. Germacrene D (21.77%), trans-ß-ocimene (14.66%), ß-pinene (9.07%), α-cadinol (8.19%) and α-pinene (6.50%) were the main components of oil determined by GC-MS. Moreover, we observed that the cytotoxic effect was increased with an increasing dose of essential oil. The EC50 value was calculated as 63.5 µg/mL. An increase in the percentage of apoptotic cells was observed after treatment of Caco-2 cells with S. syriaca essential oil revealed by image-based cytometry. A nearly 6-fold increase was found in annexin-positive cells after treatment. In terms of mRNA levels, RT-PCR analysis indicated that, although Bax and Caspase-3 were increased, Bcl-2 was decreased after oil treatment. According to our results, S. syriaca essential oil has promising phytochemicals that might be useful in cancer treatment due to their relatively cytotoxic and apoptotic activities in Caco-2 cells.

New iridium bis-terpyridine complexes: synthesis, characterization, antibiofilm and anticancer potentials.

This study represents synthesis, characterization, screening of antibiofilm efficacy, and cytotoxicity of iridium bis-terpyridine complexes. The complexes were characterized by NMR, MS, FTIR, UV/Visible, and fluorescence spectroscopies. The efficacy of biofilm inhibition and eradication of iridium complexes was evaluated using a crystal violet assay test and verified by fluorescence microscopy. Cytotoxicity and apoptosis analysis of iridium complexes were determined in this study. The results of our study revealed that three iridium complexes had the potential to inhibit biofilm formation and moderate the ability to destroy pre-formed biofilm of S. aureus ATCC 29,213. 250 µM concentration of synthesized complexes showed the highest antibiofilm activity (75% for Ir1, 90% for Ir2, and 71% for Ir3). The significant inhibition obtained at 6.25 µM concentration of Ir2 and Ir3 revealed the potential of our samples. Also, Ir1 and Ir2 complexes had a good capacity to destroy pre-formed biofilm. The results clearly showed that iridium complexes have cytotoxic activity towards colon cancer (Caco-2) and liver cancer (HepG2) cell lines without affecting non-cancerous cells (HEK293) at applied doses. Moreover, tested compounds induced apoptosis in these cancer cells. All of these results showed that iridium complexes had possessed the ability to inhibit or destroy pre-formed biofilm and could be developed as an effective agent against bacterial biofilms. Moreover, these pure substances may have valuable anti-cancer activity and it should be confirmed with further studies for therapeutic effects.

Identification of 3-Bromo-1-Ethyl-1H-Indole as a Potent Anticancer Agent with Promising Inhibitory Effects on GST Isozymes.

BACKGROUND: Indole-based heterocyclic compounds play important roles in pharmaceutical chemistry due to their unexpected biological and pharmacological properties. OBJECTIVE: Herein, we describe novel biological properties (antioxidant, antimicrobial and anti-cancer) of 3- bromo-1-ethyl-1H-indole (BEI) structure. METHODS: BEI was synthesized from 1-Methyl-2-phenylindole and N-bromosuccinimide and was characterized by using 1H and 13C NMR. Cytotoxicity was determined by MTT assay. Apoptosis analysis of BEI was determined by Arthur™ image-based Cytometer. Different methods were applied to assess the antioxidant activity of BEI. Molecular docking studies were conducted to determine the interactions of bonding between GST isozymes and BEI. RESULTS: According to the antioxidant and antimicrobial activity assays, BEI compound showed reduced total antioxidant activity compared to the Trolox standard, whereas it showed moderate antimicrobial activity against Aspergillus niger and Phytophora eryhtrospora. Notably, the BEI compound demonstrated substantial selective cytotoxicity for the first time towards cancer cell lines, and there existed a significant decrease in the percentage of live cells treated with BEI, in comparison to the control ones. Interestingly, BEI exhibited a promising glutathione S-transferase isozymes inhibition. CONCLUSION: The results of this study suggest that BEI seems to be a promising molecule to be used in the design of new anti-cancer agents that provide superiority to present commercial anti-cancer drugs.