Progress of Photoantibiotics in Overcoming Antibiotic Resistance.

Antibiotic resistance has emerged as a global public health crisis in the 21 century, leading to treatment failures. To address this issue, the medical and pharmaceutical sectors are confronted with two challenges: i) finding potent new antimicrobial agents that would work against resistant-pathogens, and ii) developing conceptually new or unconventional strategies by which a particular antibiotic would remain effective persistently. Photopharmacology with the aid of reversibly controllable light-active antibiotics that we call "photoantibiotics" shows great promise to meet the second challenge, which has inspired many research laboratories worldwide to align their research in inventing or developing such antibiotics.

Photoisomerization and Light-Controlled Antibacterial Activity of Fluoroquinolone-Azoisoxazole Hybrids.

Photopharmacology holds a huge untapped potential to locally treat diseases involving photoswitchable drugs via the elimination of drugs' off-target effects. The growth of this field has created a pressing demand to develop such light-active drugs. We explored the potential for creating photoswitchable antibiotic hybrids by attaching pharmacophores norfloxacin/ciprofloxacin and azoisoxazole (photoswitch).

Visible-Light-Sensitive Photoliquefiable Arylazoisoxazoles for the Solar Energy Conversion, Storage and Controlled-Release of Heat at Room Temperature or Lower Temperatures.

The photoswitchable MOlecular Solar Thermal (MOST) energy storage systems that are capable of exhibiting high energy storage densities are found to suffer from the poor cyclability, the use of less abundant UV light of the solar spectrum, or reduced charging/discharging rates and poor photoconversions in solid states. Herein, we have designed and readily synthesized a novel set of para-thioalkyl substituted arylazoisoxazoles, that undergo high trans-cis and cis-trans photoconversions under visible light, and show fast charging/discharging and impressive cyclability. Remarkably, the presence of C6-or C10-thioalkyl chainin photochromes permitted reversible solid-liquid phase transition with the formation of cis-enriched charged states by 400 nm light irradiation and trans-enriched discharged states by 530 nm light at various temperatures (10-35 °C).

Direct Growth Control of Antibiotic-Resistant Bacteria Using Visible-Light-Responsive Novel Photoswitchable Antibiotics.

In addition to the discovery of new (modified) potent antibiotics to combat antibiotic resistance, there is a critical need to develop novel strategies that would restrict their off-target effects and unnecessary exposure to bacteria in our body and environment. We report a set of new photoswitchable arylazopyrazole-modified norfloxacin antibiotics that present a high degree of bidirectional photoisomerization, impressive fatigue resistance and reasonably high cis half-lives. The irradiated isomers of most compounds were found to exhibit nearly equal or higher antibacterial activity than norfloxacin against Gram-positive bacteria.

Photoswitchable Antibiotic Hybrids: Spacer Length-Dependent Photochemical Control of Antibacterial Activity.

Photopharmacology holds huge potential for the permanent (long-term) eradication of antibiotic resistance by the application of photoswitchable antibiotics. To construct such antibiotics, various methods have been employed to modify known antibiotics with photoswitches, such that the irradiated state shows activity comparable to or higher than that of the parent antibiotic and that a large activity difference between irradiated and nonirradiated states is achieved. However, most of those methods are ineffective when dealing with more than one drug with dissimilar structures.

Photoisomerization of 2-Arylazoimidazoles under Visible Light: Identifying a Predictive Tool to Anticipate and Tune Likely Photoswitching Performance and Cis Half-Life.

Azopyrazoles are an emerging class of photoswitches, whereas analogous azoimidazole-based switches are unable to draw much attention because of their short cis half-lives, poor cis-trans photoreversion yields, and toxic ultraviolet (UV) light-assisted isomerization. A series of 24 various aryl-substituted -methyl-2-arylazoimidazoles were synthesized, and their photoswitching performances and cis-trans isomerization kinetics were thoroughly investigated experimentally and theoretically. -π-donor-substituted azoimidazoles with highly twisted T-shaped cis conformations showed nearly complete bidirectional photoswitching, whereas di--substituted switches exhibited very long cis half-lives (days-years) with nearly ideal T-shaped conformations.

Near-Complete Bidirectional Photoisomerization of -Dialkylamino-Substituted Arylazopyrazoles under Violet and Green or Red Lights.

-Dimethylamine- and -pyrrolidine-substituted arylazopyrazoles display very high to near-quantitative or quantitative bidirectional isomerization under violet and green or red lights in both polar (DMSO and DMSO/aqueous buffer, pH 7.5) and nonpolar solvents. These switches confer a reasonable thermal stability to their -states ( ≈ 4-7 h in DMSO and DMSO/buffer) and also show a high level of resistance to photobleaching and an impressive stability to reduction by glutathione.

Robust bi-directional photoswitching of thiomethyl substituted arylazopyrazoles under visible light.

Mono-ortho- and para-thiomethyl-substituted arylazopyrazoles show substantial absorbance in visible wavelengths, enabling very high to near-quantitative forward and reverse isomerization in DMSO and aqueous solution by visible light. cis isomers display excellent thermal stability (∼3 days, 27 °C). Additionally, these switches possess good photostability and are resistant to reduction by glutathione.