Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.     

Surface modification of multiwalled carbon nanotubes via surface RAFT copolymerization method and capecitabine-loaded anticancer hydrogel for controlled drug delivery in stomach

ABSTRACT

In our work, reversible addition-fragmentation chain transfer (RAFT)/carbon nanotube (CNT)/acrylic acid (AA)/acrylamide (AAm) nanocomposite was synthesized by living radical polymerization. The structure and surface morphology of the synthesized RAFT-CNT-Hydrogel nanocomposites were analyzed by FTIR, ¹HNMR, SEM, TEM, XRD, and TGA/DTG techniques. The results indicated that PAA/AAm chains grafted with CNT by RAFT polymerization. RAFT-CNT-Hydrogel nanocomposites for drug release investigated in different buffers resulted in a strong pH-sensitive behavior. In total, the obtained hydrogel drug-delivery systems are presented a proper effect versus stomach cancer in vitro and in vivo, and it can be used as candidates for controlled release of anticancer drugs in stomach with exalted remedial agents.     

Design,Synthesis and Biological Evaluation of Steroidal Glycoconjugates as Potential Antiproliferative Agents

To systematically evaluate the impact of neoglycosylation upon the anticancer activities and selectivity of steroids, four series of neoglycosides of diosgenin, pregnenolone, dehydroepiandrosterone and estrone were designed and synthesized according to the neoglycosylation approach. The structures of all the products were elucidated by NMR analysis, and the stereochemistry of C20-MeON-pregnenolone was confirmed by crystal X-ray diffraction. The compounds′ cytotoxicity on five human cancer cell lines was evaluated using a Cell Counting Kit-8 assay, and structure–activity relationships (SAR) are discussed. 2-deoxy-d -glucoside 5 k displayed the most potent antiproliferative activities against HepG2 cells with an IC₅₀ value of 1.5 μM. Further pharmacological experiments on compound 5 k on HepG2 cells revealed that it could cause morphological changes and cell-cycle arrest at the G0/G1 phase and then induced the apoptosis, which might be associated with the enhanced expression of high-mobility group Box 1 (HMGB1). Taken together, these findings prove that the neoglycosylation of steroids could be a promising strategy for the discovery of potential antiproliferative agents.     

Apoptotic Effects of Anthocyanins from Vitis coignetiae Pulliat Are Enhanced by Augmented Enhancer of the Rudimentary Homolog (ERH) in Human Gastric Carcinoma MKN28 Cells

Evidence suggests that augmented expression of a certain gene can influence the efficacy of targeted and conventional chemotherapies. Here, we tested whether the high expression of enhancer of the rudimentary homolog (ERH), which serves as a prognostic factor in some cancers, can influence the efficacy of anthocyanins isolated from fruits of Vitis coignetiae Pulliat, Meoru in Korea (AIMs) on human gastric cancer cells. The anticancer efficacy of AIMs was augmented in ERH-transfected MKN28 cells (E-MKN28 cells). Molecularly, ERH augmented AIM-induced caspase-dependent apoptosis by activating caspase-3 and -9. The ERH-augmented apoptotic effect was related to mitochondrial depolarization and inhibition of antiapoptotic proteins, XIAP, and Bcl-2. In addition, reactive oxygen species (ROS) generation was augmented in AIMs-treated E-MKN28 cells compared to AIMs-treated naïve MKN28 cells. In conclusion, ERH augmented AIM-induced caspase-dependent mitochondrial-related apoptosis in MKN28 cells. A decrease in expression of Bcl-2 and subsequent excessive ROS generation would be the mechanism for ERH-augmented mitochondrial-related apoptosis in AIMs-treated MKN28 cells. A decrease in expression of XIAP would be another mechanism for ERH-augmented caspase-dependent apoptosis in AIMs-treated MKN28 cells.     

Revisiting Platinum-Based Anticancer Drugs to Overcome Gliomas

Although there are many patients with brain tumors worldwide, there are numerous difficulties in overcoming brain tumors. Among brain tumors, glioblastoma, with a 5-year survival rate of 5.1%, is the most malignant. In addition to surgical operations, chemotherapy and radiotherapy are generally performed, but the patients have very limited options. Temozolomide is the most commonly prescribed drug for patients with glioblastoma. However, it is difficult to completely remove the tumor with this drug alone. Therefore, it is necessary to discuss the potential of anticancer drugs, other than temozolomide, against glioblastomas. Since the discovery of cisplatin, platinum-based drugs have become one of the leading chemotherapeutic drugs. Although many studies have reported the efficacy of platinum-based anticancer drugs against various carcinomas, studies on their effectiveness against brain tumors are insufficient. In this review, we elucidated the anticancer effects and advantages of platinum-based drugs used in brain tumors. In addition, the cases and limitations of the clinical application of platinum-based drugs are summarized. As a solution to overcome these obstacles, we emphasized the potential of a novel approach to increase the effectiveness of platinum-based drugs.     

Preparation and Bioactivity of Iridium(III) Phenanthroline Complexes with Halide Ions and Pyridine Leaving Groups

A series of half-sandwich structural iridium(III) phenanthroline (Phen) complexes with halide ions (Cl⁻, Br⁻, I⁻) and pyridine leaving groups ([(η⁵-Cp^X)Ir(Phen)Z](PF₆)_n, Cp^x: electron-rich cyclopentadienyl group, Z: leaving group) have been prepared. Target complexes, especially the Cp^xbiph (biphenyl-substituted cyclopentadienyl)-based one, showed favourable anticancer activity against human lung cancer (A549) cells; the best one ( Ir8 ) was almost five times that of cisplatin under the same conditions. Compared with complexes involving halide ion leaving groups, the pyridine-based one did not display hydrolysis but effectively caused lysosomal damage, leading to accumulation in the cytosol, inducing an increase in the level of intracellular reactive oxygen species and apoptosis; this indicated an anticancer mechanism of oxidation. Additionally, these complexes could bind to serum albumin through a static quenching mechanism. The data highlight the potential value of half-sandwich iridium(III) phenanthroline complexes as anticancer drugs.     

福莫司汀的合成

以亚磷酸三乙酯为起始原料．经酰化、缩合、还原、酰化、亚硝化反应，合成了福莫司汀，结构经核磁共振氢谱、经红外确证，总收率32．8％。     

Synthesis of Organotin Polyamine Ethers Containing Acyclovir and their Preliminary Anticancer and Antiviral Activity

Organotin polyamine ethers containing acyclovir in their backbone were synthesized in moderate to high yield employing the aqueous interfacial polycondensation system. The products are high molecular weight polymers. Infrared spectroscopy of the products shows new bands characteristic of the formation of Sn–N and Sn–O bonds consistent with the proposed structure. MALDI-TOF MS below 2000 Da shows the presence of organotin and acyclovir units containing these two moieties. The products show moderate inhibition of a number of cancer cell lines and exhibit the ability to inhibit a number of viruses, particularly the herpes simplex virus-1 and varicella zoster virus that are responsible for herpes, chicken pox and shingles.