Design and synthesis of purine connected piperazine derivatives as novel inhibitors of Mycobacterium tuberculosis

Konduri, Srihari; Prashanth, Jyothi; Krishna, Vagolu Siva; Sriram, Dharmarajan; Behera, J. N.; Siegel, Dionicio; Rao, Koya Prabhakara

doi:10.1016/j.bmcl.2020.127512

Cited by 31 publications

(22 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The new approach to drug discovery is the incorporation of various biologically active molecules in a single hybrid framework may allow changes in the biological properties of the hybrid molecule when compared to the parent molecule [27] . In continuation of our ongoing interest, [15,16,23–25] in the present study, we are amalgamating the urea and thiourea precursors with pharmaceutical important Sacubitril moiety and further explored their anti‐TB activity.…”

Section: Introductionmentioning

confidence: 94%

See 1 more Smart Citation

Sacubitril‐Based Urea and Thiourea Derivatives as Novel Inhibitors for Anti‐Tubercular against Dormant Tuberculosis

et al. 2021

Self Cite

View full text Add to dashboard Cite

In the present study, we have attempted to identify Sacubitril derivatives as lead compounds for dormant tuberculosis. A total of twenty‐one compounds belongs to a series of the Sacubitril derivatives 5(a–u) were synthesized using (2R,4S)‐5‐([1,1′‐biphenyl]‐4‐yl)‐4‐(amino)‐2‐methylpentanoic acid ethyl ester hydrochloride with different isocyanates and isothiocyanates. All the compounds structures were determined by 1H & 13C NMR spectroscopy, mass spectrometry, and CHN analysis. Compound, 5 r, the structure confirmed by single‐crystal X‐ray diffraction analysis (SXRD). The newly synthesized compounds were screened for their in vitro antituberculosis activity (anti‐TB) against dormant Mycobacterium tuberculosis H37Rv (ATCC27294). Among the twenty‐one compounds, 5 p and 5 q were exhibited good potent anti‐TB activity compared to the standard drug Ethambutol. Further, the anti‐TB activities of the compounds (5 p and 5 q) were evaluated against M. tuberculosis (Mtb) using the nutrient starvation model (NSM). Moreover, these two compounds, 5 p and 5 q have shown significant inhibition of growth of Mtb as compared to the control. To determine the toxicity nature, the potent anti‐TB active compounds were evaluated against RAW 264.7 cells. Further, the anti‐TB activities of all these compounds have shown a good correlation to their in‐silico molecular docking analysis by exhibiting strong interactions with the inhibitor Mur‐B.

show abstract

Section: Introductionmentioning

confidence: 94%

“…On the other hand, urea and thiourea are, the more polar, metabolically stable important precursors and are also known to possess potent anti‐mycobacterial activity [11–16] . Several derivatives of these compounds have been potentially identified to possess potent antituberculosis activity in the literature [17,18] .…”

Section: Introductionmentioning

confidence: 99%

Sacubitril‐Based Urea and Thiourea Derivatives as Novel Inhibitors for Anti‐Tubercular against Dormant Tuberculosis

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Methyl-6-(2-(adamantane-1-carboxamido) phenyl)-4amino-3-chloropicolinate (8). Compound 7 (38 mg, 0.14 mmol) was initially dissolved in DCM (2.0 mL) solvent and cooled to 10 −20 °C.…”

Section: ■ Conclusionmentioning

confidence: 99%

Design and Synthesis of “Chloropicolinate Amides and Urea Derivatives” as Novel Inhibitors for Mycobacterium tuberculosis

et al. 2021

Self Cite

View full text Add to dashboard Cite

A series of 30 novel diamino phenyl chloropicolinate fettered carboxamides, urea, and thiourea derivatives were synthesized by coupling of methyl 4-amino-6-(2-aminophenyl)-3-chloropyridine-2-carboxylate with different acid chlorides, urea, and thiourea moieties, respectively. All of these compounds were characterized by 1H and 13C nuclear magnetic resonance spectroscopy, CHN analysis, and high-resolution mass spectra for confirmation of the structures. Two compounds were also characterized by single-crystal X-ray diffraction analysis to confirm the structures obtained by spectral analysis. All these 30 compounds were tested for their in vitro antimycobacterial activity using the microplate alamar blue assay method against Mycobacterium tuberculosis. Five compounds have shown good minimum inhibitory concentration (MIC) values with low cytotoxicity when compared with the reference drugs. Moreover, some of the compounds have high MIC values compared with isoniazid, rifampicin, and so forth and also had shown good reign in the spread of bacteria by the nutrient starvation model. These antimycobacterial activity results have shown a good correlation with molecular docking model analysis with the inhibitors MurB by exhibiting strong interactions. Some of these compounds could be promising candidates against M. tuberculosis for future preclinical agent drug development.

show abstract

“…Among all the compounds, analog 11 with MIC of 12.46 μM against MTB H37Rv strain was the most potent. 24 Raju and his group reported novel pyrazole sulfonamides as anti-TB agents. From this series, compound 12 with MIC of 6.25 μg mL −1 against MTB H37Rv strain was the most active one.…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a]pyridine analogues

et al. 2022

View full text Add to dashboard Cite

show abstract

Design and synthesis of purine connected piperazine derivatives as novel inhibitors of Mycobacterium tuberculosis

Cited by 31 publications

References 37 publications

Sacubitril‐Based Urea and Thiourea Derivatives as Novel Inhibitors for Anti‐Tubercular against Dormant Tuberculosis

Sacubitril‐Based Urea and Thiourea Derivatives as Novel Inhibitors for Anti‐Tubercular against Dormant Tuberculosis

Design and Synthesis of “Chloropicolinate Amides and Urea Derivatives” as Novel Inhibitors for Mycobacterium tuberculosis

Design, synthesis and anti-mycobacterial evaluation of imidazo[1,2-a]pyridine analogues

Contact Info

Product

Resources

About