Mycobacterium tuberculosis lysine-ɛ-aminotransferase a potential target in dormancy: Benzothiazole based inhibitors

Reshma, Rudraraju Srilakshmi; Jeankumar, Variam Ullas; Kapoor, Nidhi; Saxena, Shalini; Bobesh, Karyakulam Andrews; Astakala, Rishi Vachaspathy; Kolattukudy, Pappachan E.; Sriram, Dharmarajan

doi:10.1016/j.bmc.2017.03.053

Cited by 25 publications

(12 citation statements)

References 21 publications

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“…The acetonitrile anion reacts rapidly with the carbonyl compound to form an enol intermediate, which subsequently transforms into acrylonitrile in a basic medium (such as piperidine, potassium hydroxide, sodium hydroxide, potassium carbonate, triethylamine, or alkali metal alkoxides) and polar solvents (such as ethanol, methanol, or tetrahydrofuran). [ 59,61–66 ]…”

Section: Synthetic Strategies Of Acrylonitrilesmentioning

confidence: 99%

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Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Tan

Zengin

2021

Archiv der Pharmazie

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Acrylonitrile is a fascinating scaffold widely found in many natural products, drugs, and drug candidates with various biological activities. Several drug molecules such as entacapone, rilpivirine, teriflunomide, and so forth, bearing an acrylonitrile moiety have been marketed. In this review, diverse synthetic strategies for constructing desired acrylonitriles are discussed, and the different biological activities and medicinal significance of various acrylonitrile derivatives are critically evaluated. The information gathered is expected to provide rational guidance for the development of clinically useful agents from acrylonitriles.

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Section: Synthetic Strategies Of Acrylonitrilesmentioning

confidence: 99%

“…In addition, compound 70 induced significant log reduction of 2.9‐ and 2.3 log‐fold at a concentration of 10 mg/ml against nutrient‐starved and biofilm‐forming mycobacteria. [ 66 ]…”

Section: Biological Activities Of Acrylonitrilesmentioning

confidence: 99%

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Tan

Zengin

2021

Archiv der Pharmazie

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“…Selected scaffolds were further explored and optimized, generating compounds with potent IC50 for the enzyme and significant inhibition against nutrient starved bacilli. The most promising compounds were compound 15 (Figure 6), with a 2.8-log bacterial reduction and an IC50 of 1.22 µM; compound 16 (Figure 6), with a bacterial reduction of over 2-log and an IC50 of 0.81 µM; and compound 17 (Figure 6), with a 2.9-log reduction in bacterial count and IC50 of 2.62 µM [169][170][171].…”

Section: Lysine ε-Aminotransferasementioning

confidence: 99%

Addressing Latent Tuberculosis: New Advances in Mimicking the Disease, Discovering Key Targets, and Designing Hit Compounds

Campaniço

Harjivan

Warner

et al. 2020

IJMS

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Despite being discovered and isolated more than one hundred years ago, tuberculosis (TB) remains a global public health concern arch. Our inability to eradicate this bacillus is strongly related with the growing resistance, low compliance to current drugs, and the capacity of the bacteria to coexist in a state of asymptomatic latency. This last state can be sustained for years or even decades, waiting for a breach in the immune system to become active again. Furthermore, most current therapies are not efficacious against this state, failing to completely clear the infection. Over the years, a series of experimental methods have been developed to mimic the latent state, currently used in drug discovery, both in vitro and in vivo. Most of these methods focus in one specific latency inducing factor, with only a few taking into consideration the complexity of the granuloma and the genomic and proteomic consequences of each physiological factor. A series of targets specifically involved in latency have been studied over the years with promising scaffolds being discovered and explored. Taking in account that solving the latency problem is one of the keys to eradicate the disease, herein we compile current therapies and diagnosis techniques, methods to mimic latency and new targets and compounds in the pipeline of drug discovery.

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“…Benzothiazole derivatives have attracted attention over a long period of time because of their wide spectrum of biological activities and the benzothiazole framework remains today an important scaffold for the design and synthesis of active molecules (Gill et al, 2015;Reshma et al, 2017;Thakkar et al, 2017;Dar et al, 2016). Among recent reports on benzothiazole derivatives are those on 2-arylidenehydrazinylbenzothiazoles, which include anti-tumour activities (Lindgren et al, 2014;Nogueira et al, 2010;Katava et al, 2017) and anti-tuberculosis activity against M. tuberculosis ATTC 27294 (Pinheiro et al, 2019); crystal structure determinations have also been included in each of these studies.…”

Section: Chemical Contextmentioning

confidence: 99%

N′-(1,3-Benzothiazol-2-yl)benzenesulfonohydrazide: crystal structure, Hirshfeld surface analysis and computational chemistry

et al. 2019

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The asymmetric unit of the title compound, C13H11N3O2S2, comprises two independent molecules (A and B); the crystal structure was determined by employing synchrotron radiation. The molecules exhibit essentially the same features with an almost planar benzothiazole ring (r.m.s. deviation = 0.026 and 0.009 Å for A and B, respectively), which forms an inclined dihedral angle with the phenyl ring [28.3 (3) and 29.1 (3)°, respectively]. A difference between the molecules is noted in a twist about the N—S bonds [the C—S—N—N torsion angles = −56.2 (5) and −68.8 (5)°, respectively], which leads to a minor difference in orientation of the phenyl rings. In the molecular packing, A and B are linked into a supramolecular dimer via pairwise hydrazinyl-N—H...N(thiazolyl) hydrogen bonds. Hydrazinyl-N—H...O(sulfonyl) hydrogen bonds between A molecules assemble the dimers into chains along the a-axis direction, while links between centrosymmetrically related B molecules, leading to eight-membered {...HNSO}2 synthons, link the molecules along [001]. The result is an undulating supramolecular layer. Layers stack along the b-axis direction with benzothiazole-C—H...O(sulfonyl) points of contact being evident. The analyses of the calculated Hirshfeld surfaces confirm the relevance of the above intermolecular interactions, but also serve to further differentiate the weaker intermolecular interactions formed by the independent molecules, such as π–π interactions. This is also highlighted in distinctive energy frameworks calculated for the individual molecules.

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Mycobacterium tuberculosis lysine-ɛ-aminotransferase a potential target in dormancy: Benzothiazole based inhibitors

Cited by 25 publications

References 21 publications

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Insights into the chemistry and therapeutic potential of acrylonitrile derivatives

Addressing Latent Tuberculosis: New Advances in Mimicking the Disease, Discovering Key Targets, and Designing Hit Compounds

N′-(1,3-Benzothiazol-2-yl)benzenesulfonohydrazide: crystal structure, Hirshfeld surface analysis and computational chemistry

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