| [Download PDF]
|Year : 2017 | Volume
| Issue : 3 | Page : 221--222
Phulen Sarma, Bikash Medhi
Department of Pharmacology, PGIMER, Chandigarh, India
Research Block B, 4th Floor, Room No. 4043, Postgraduate Institute of Medical Education and Research, Chandigarh - 160 012
|How to cite this article:|
Sarma P, Medhi B. Photopharmacology.Indian J Pharmacol 2017;49:221-222
|How to cite this URL:|
Sarma P, Medhi B. Photopharmacology. Indian J Pharmacol [serial online] 2017 [cited 2018 Apr 21 ];49:221-222
Available from: http://www.ijp-online.com/text.asp?2017/49/3/221/215730
Selectivity to target tissue/site is a problem with many of the drugs; many of the sites of drug actions (enzymes, receptors, ion channels, and carrier molecules) are expressed in other sites/tissues/organs and the action of drugs in these sites leads to intolerable side effects. Selectivity to target site/organ can be increased by various strategies and photopharmacology is one such strategy. Photopharmacology provides us an external photoswitch to control off-target site drug activity, and thus helps to attain selective biological activity and ameliorating off-target toxicity and resultant side effects.,,
The concept of phototherapy is more than 100 years old. Niels Finsen treated lupus with controlled exposure of his patients to sunlight (heliotherapy). Finsen then designed an artificial light source for the treatment of psoriasis patients. This event became a landmark as it marked the birth of modern phototherapy for which he was awarded the Nobel Prize in 1903.
Photopharmaceutical agents are developed by incorporating photoresponsive switches to drugs, enabling the change of biological configuration of drugs on exposure to light of special wavelength and subsequent biological activation. These photoswitches may bind to their targets by both noncovalent (also known as photochromatic ligands) and covalent interactions (also known as photoswitchable-tethered ligands).,,
One of the important photoswitches is azobenzenes, trans-azobenzene gets converted into cis-azobenzene on exposure to ultraviolet (UV) light and the process is reversible when exposed to light of visible range. Other azobenzenes, such as Hecht's o-fluoroazobenzes or Fuchter's arylazopyrazoles, also act as photoswitches. Being relatively small, azobenzenes can be easily incorporated into a drug-like molecule of low molecular weight.
Photoactivation may be achieved externally or internally. The photoswitch can be activated at desired site with high spatiotemporal precision using the specific wavelength required and thus the rest of the parts of the body potentially do not get exposed to the harmful effects of the drug.,,
Photoactivation can be reversed with subsequent application of a different wavelength of light or it can also occur spontaneously following a thermal process. This allows us to use light as an external controlling factor to modulate drug activity as required.,
In photodynamic therapy, light-mediated generation of singlet oxygen is used for ablating tissue. As these free radicals are short lived, the net effect is reversible, highly spatially selective, and of short duration. Other potential fields of application are optogenetics, photoactivated metal complexes, bioactive compounds, and photoactivated molecules (psoralens).
These photopharmacologic agents expose us toward a great avenue; highly selective target site action can be achieved as light can be delivered with very high spatiotemporal precision.,, On the other hand, it possesses some challenges too. Delivery of photons to target tissues poses as the major challenge as lower energy photons from the UV/visible range get scattered in tissue and get absorbed by endogenous chromophores, which severely limits the penetrability of light. This process also can cause photodamage to the cells, leading to manifestations of UV light toxicity. Depending on the accessibility and penetrability by light, tissues are classified as class 1 to class 5, with high class tissue being more difficult to light penetration and subsequent requirement of major/minor operation.
This area is advancing rapidly and the field is covering antimicrobials (ciprofloxacin-photoswitch conjugates), photoswitchable amidohydrolase inhibitors, diabetes (Optical Control of Insulin Secretion Using an Incretin Switch), fourth-generation photoswitchable sulfonylurea JB253, anticancer (photoswitchable histone deacetylase inhibitors), red light-activated ruthenium-caged nicotinamide phosphoribosyltransferase inhibitor, azobenzene-containing photoswitchable proteasome inhibitors, etc., and much more field is being explored.
This field of photopharmacology is rapidly advancing in the past few years. Newer and promising avenues are emerging. With advances in optical technologies and better photoswitch technologies, we can have better spatiotemporal control of drug action and hence we can expect enhanced safety and efficacy of the photopharmaceutical agents compared to their conventional counterparts. Hope to see many clinical studies on photopharmacological agents very soon.
|1||Lerch MM, Hansen MJ, van Dam GM, Szymanski W, Feringa BL. Emerging targets in photopharmacology. Angew Chem Int Ed Engl 2016;55:10978-99.|
|2||Velema WA, Szymanski W, Feringa BL. Photopharmacology: Beyond proof of principle. J Am Chem Soc 2014;136:2178-91.|
|3||Broichhagen J, Frank JA, Trauner D. A roadmap to success in photopharmacology. Acc Chem Res 2015;48:1947-60.|
|4||Gasparro FP, Chan G, Edelson RL. Phototherapy and photopharmacology. Yale J Biol Med 1985;58:519-34.|
|5||Velema WA, Hansen MJ, Lerch MM, Driessen AJ, Szymanski W, Feringa BL, et al. Ciprofloxacin-photoswitch conjugates: A facile strategy for photopharmacology. Bioconjug Chem 2015;26:2592-7.|
|6||Weston CE, Krämer A, Colin F, Yildiz Ö, Baud MG, Meyer-Almes FJ, et al. Toward photopharmacological antimicrobial chemotherapy using photoswitchable amidohydrolase inhibitors. ACS Infect Dis 2017;3:152-61.|
|7||Broichhagen J, Podewin T, Meyer-Berg H, von Ohlen Y, Johnston NR, Jones BJ, et al. Optical control of insulin secretion using an incretin switch. Angew Chem Int Ed Engl 2015;54:15565-9.|
|8||Mehta ZB, Johnston NR, Nguyen-Tu MS, Broichhagen J, Schultz P, Larner DP, et al. Remote control of glucose homeostasis in vivo using photopharmacology. Sci Rep 2017;7:291.|
|9||Szymanski W, Ourailidou ME, Velema WA, Dekker FJ, Feringa BL. Light-controlled histone deacetylase (HDAC) inhibitors: Towards photopharmacological chemotherapy. Chemistry 2015;21:16517-24.|
|10||Lameijer LN, Ernst D, Hopkins SL, Meijer MS, Askes SH, Le Dévédec SE, et al. A red light-activated ruthenium-caged NAMPT inhibitor remains phototoxic in hypoxic cancer cells. Angew Chem Int Ed Engl 2017. [Epub ahead of print].|
|11||Blanco B, Palasis KA, Adwal A, Callen DF, Abell AD. Azobenzene-containing photoswitchable proteasome inhibitors with selective activity and cellular toxicity. Bioorg Med Chem 2017. [Epub ahead of print].|