Light-induced disruption of an acyl hydrazone link as a novel strategy for drug release and activation: isoniazid as a proof-of-concept case

Nunes, Edinaira; Villela, Anne Drumond; Basso, Luiz Augusto; Teixeira, Edson Holanda; Andrade, Alexandre Lopes; Vasconcelos, Mayron Alves de; Neto, Luiz Nascimento; Gondim, Ana C. S.; Diógenes, Izaura C.N.; Romo, Adolfo I. B.; Nascimento, Otaciro Rangel; Zampieri, Dávila; Paulo, Tércio F.; Carvalho, Idalina M.M. de; Lopes, Luiz Gonzaga de França; Sousa, Eduardo Henrique Silva

doi:10.1039/c9qi01172b

Cited by 13 publications

(6 citation statements)

References 45 publications

(42 reference statements)

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“…Similarly, methylene blue and alkoxyanthracene were used as a photosensitizer and a cleavable group, respectively, to disrupt micelles loaded with a chemotherapeutic agent. 1448 Other singlet-oxygen sensitive groups including thioketals, 1449 − 1462 thioethers, 1463 imidazoles, 1464 indolizines, 1465 and hydrazones, 1466 as well as selenium- 1467 − 1477 and tellurium-containing 1478 − 1480 moieties have also been used for uncaging. A qualitatively different photosensitizer, TiO 2 nanotube-doped PbS quantum dots combined with S -nitrosocysteine, was found to generate singlet oxygen upon irradiation at <600 nm, leading to the release of nitric oxide ( Scheme 94 ).…”

Section: Photosensitized Release: From Small Molecules To Nanoparticlmentioning

confidence: 99%

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

et al. 2020

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Photoactivatable (alternatively, photoremovable, photoreleasable, or photocleavable) protecting groups (PPGs), also known as caged or photocaged compounds, are used to enable non-invasive spatiotemporal photochemical control over the release of species of interest. Recent years have seen the development of PPGs activatable by biologically and chemically benign visible and near-infrared (NIR) light. These long-wavelength-absorbing moieties expand the applicability of this powerful method and its accessibility to non-specialist users. This review comprehensively covers organic and transition metal-containing photoactivatable compounds (complexes) that absorb in the visible- and NIR-range to release various leaving groups and gasotransmitters (carbon monoxide, nitric oxide, and hydrogen sulfide). The text also covers visible- and NIR-light-induced photosensitized release using molecular sensitizers, quantum dots, and upconversion and second-harmonic nanoparticles, as well as release via photodynamic (photooxygenation by singlet oxygen) and photothermal effects. Release from photoactivatable polymers, micelles, vesicles, and photoswitches, along with the related emerging field of photopharmacology, is discussed at the end of the review.

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Section: Photosensitized Release: From Small Molecules To Nanoparticlmentioning

confidence: 99%

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

et al. 2020

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Section: Devs and Dost-a Short Historymentioning

confidence: 97%

“…The overall mechanism of functioning of this two(three)-component system may be more complex than expected [25]. There is a series of other protein partners, protein modifiers (serine threonine kinase, acetylation) and cross-talks with other sensing systems involved, making this whole story complex, as discussed elsewhere [25]. Nevertheless, there are many opportunities ahead to unfold these details and find new applications for these systems either as drug targets or biological tools, etc.…”

Section: Devs and Dost-a Short Historymentioning

confidence: 99%

“…These intricate arrangements have allowed nature to come up with many outstanding biological responses, regulating multiple processes as important as blood pressure, biological clock, nitrogen fixation, dormancy, bacterial biofilm, RNA degradation, virulence, among others. Unfortunately, a detailed structural mechanism of the signal transduction processes is still mainly lacking, but some important insights have emerged, as mentioned briefly here and in detail elsewhere [1,2,20,[25][26][27][28][29].…”

Section: Introductionmentioning

confidence: 99%

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Heme-Based Gas Sensors in Nature and Their Chemical and Biotechnological Applications

Gondim

Guimarães

Sousa

2022

BioChem

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Sensing is an essential feature of life, where many systems have been developed. Diatomic molecules such as O2, NO and CO exhibit an important role in life, which requires specialized sensors. Among the sensors discovered, heme-based gas sensors compose the largest group with at least eight different families. This large variety of proteins also exhibits many distinct ways of sensing diatomic molecules and promote a response for biological adaptation. Here, we briefly describe a story of two impressive systems of heme-based oxygen sensors, FixL from Rhizobium and DevS(DosS)/DosT from Mycobacterium tuberculosis. Beyond this, we also examined many applications that have emerged. These heme-based gas sensors have been manipulated to function as chemical and biochemical analytical systems to detect small molecules (O2, CO, NO, CN−), fluorophores for imaging and bioanalysis, regulation of processes in synthetic biology and preparation of biocatalysts among others. These exciting features show the robustness of this field and multiple opportunities ahead besides the advances in the fundamental understanding of their molecular functioning.

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“…Since these processes usually require the population of ligand dissociative metal-centered ( 3 MC) states, whose direct excitation is forbidden, strain-inducing substituents are commonly inserted into Ru(II) scaffolds to lower the energy of 3 MC states and permit their thermal population. , In spite of the attractive perspectives, and in net contrast to photoactivated chemotherapy (PACT), where this strategy is gaining momentum, − the translation of such an approach in the research of new antimicrobials has been only sparingly investigated. In fact, very few examples − followed the pioneering work by Sadler and co-workers on the use of Ru(II) photocages to control the liberation of the antituberculosis drug isoniazid (INH) and, importantly, none of them inspected the antibacterial potential under the more therapeutically relevant, hypoxic conditions.…”

Section: Introductionmentioning

confidence: 99%

Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions

et al. 2023

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Ruthenium(II) polypyridyl complexes (RPCs) are gaining momentum in photoactivated chemotherapy (PACT), thanks to the possibility of overcoming the classical reliance on molecular oxygen of photodynamic therapy while preserving the selective drug activation by using light. However, notwithstanding the intriguing perspectives, the translation of such an approach in the development of new antimicrobials has been only barely considered. Herein, MTZH-1 and MTZH-2, two novel analogues of metronidazole (MTZ), a mainstay drug in the treatment of anaerobic bacterial infections, were designed and inserted in the strained ruthenium complexes [Ru(tpy)(dmp)(MTZ-1)]PF6 (Ru2) and [Ru(tpy)(dmp)(MTZ-2)]PF6 (Ru3) (tpy = terpyridine, dmp = 2,9-dimethyl-1,10-phenanthroline) (Chart 1). Analogously to the parental compound [Ru(tpy)(dmp)(5NIM)]PF6 (Ru1) (5-nitroimidazolate), the Ru(II)-imidazolate coordination of MTZ derivatives resulted in promising Ru(II) photocages, capable to easily unleash the bioactive ligands upon light irradiation and increase the antibacterial activity against Bacillus subtilis, which was chosen as a model of Gram-positive bacteria. The photoreleased 5-nitroimidazole-based ligands led to remarkable phototoxicities under hypoxic conditions (<1% O2), with the lead compound Ru3 that exhibited the highest potency across the series, being comparable to the one of the clinical drug MTZ. Besides, the chemical architectures of MTZ derivatives made their interaction with NimAunfavorable, being NimA a model of reductases responsible for bacterial resistance against 5-nitroimidazole-based antibiotics, thus hinting at their possible use to combat antimicrobial resistance. This work may therefore provide fundamental knowledge in the design of novel photoresponsive tools to be used in the fight against infectious diseases. For the first time, the effectiveness of the “photorelease antimicrobial therapy” under therapeutically relevant hypoxic conditions was demonstrated.

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Light-induced disruption of an acyl hydrazone link as a novel strategy for drug release and activation: isoniazid as a proof-of-concept case

Abstract: Photocleavage of an acyl hydrazone bridge was achieved by conjugating isoniazid to a ruthenium(ii) metal complex through the generation of singlet oxygen, which released and activated the anti-tuberculosis pro-drug isoniazid.

Cited by 13 publications

References 45 publications

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

Visible-to-NIR-Light Activated Release: From Small Molecules to Nanomaterials

Heme-Based Gas Sensors in Nature and Their Chemical and Biotechnological Applications

Ruthenium(II) Polypyridyl Complexes and Metronidazole Derivatives: A Powerful Combination in the Design of Photoresponsive Antibacterial Agents Effective under Hypoxic Conditions

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