Glycosidase-activated H2S donorsto enhance chemotherapy efficacy.

Hydrogen sulfide (H2S) plays a critical role in cancer biology. Herein, we developed a series of glycosidase-triggered hydrogen sulfide (H2S) donors by connecting sugar moieties (including glucose, galactose and mannose) to COS donors via a self-immolative spacer. In the presence of corresponding glycosidases, H2S was gradually released from these donors in PBS buffer with releasing efficiencies from 36 to 67 %. H2S release was also detected by H2S probe WSP-1 after treatment HepG2 cells with Man1. Cytotoxicities of these glycosylated H2S donors were evaluated against HepG2 by MTT assay. Among them, Man1 and Man2 exhibited an obvious reduction of cell viability in HepG2 cells, with cell viability as 37.6 % for 80 µM of Man. Consistently, significant apoptosis was observed in HepG2 cells after treatment with Man1 and Man2. Finally, We evaluated the potential of Man1 for combination therapy with doxorubicin. A synergistic effect was observed between Man1 and Doxorubicin in HepG2 and Hela cells. All these results indicated glycosidase-activated H2S donorshave promising potential for cancer therapy.

Photoactive NO hybrids with pseudo-zero-order release kinetics for antimicrobial applications.

Bacterial infection is a major threat to the health and life of humans due to the development of drug resistance, which is related to biofilm formation. Nitric oxide (NO) has emerged as an important factor in regulating biofilm formation. In order to harness the potential benefits of NO and develop effective antibacterial agents, we designed and synthesized a new class of NO hybrids in which the active scaffold benzothienoazepine was tagged with a nitroso group and further conjugated with quaternary ammoniums or phosphoniums. The temporal release of NO from these hybrids can be achieved by photoactivation. Interestingly, the NO release follows a pseudo-zero-order kinetics, which is easily determined by measuring the fluorescent benzothienoazepine or NO. Compared to the positive control ciprofloxacin, the NO hybrid with triphenyl phosphonium (TPP) exhibited more effective activity against S. aureus biofilm in darkness. Irradiation of the NO hybrid led to higher inhibition against S. aureus biofilm compared to the parental NO hybrid in darkness or the corresponding NO-released product, indicating the combined effect of NO and the NO-released product. Therefore, this new class of NO hybrids includes very promising antimicrobial agents and this work provides a new way for the design of highly effective antimicrobial agents.