Synthesis and evaluation of chromenyl barbiturates and thiobarbiturates as potential antitubercular agents

Laxmi, S. Vijaya; Reddy, Y. Thirupathi; Kuarm, B. Suresh; Reddy, P. Narsimha; Crooks, Peter A.; Rajitha, B.

doi:10.1016/j.bmcl.2011.05.055

Cited by 64 publications

(12 citation statements)

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“…Literature review also revealed that barbiturates and thiobarbiturates show antituberculosis [49], anti-diabetic and anti-bacterial properties [50].…”

mentioning

confidence: 97%

Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies

Rauf

Shahzad

Bajda

et al. 2015

Bioorganic & Medicinal Chemistry

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“…Literature review also revealed that barbiturates and thiobarbiturates show antituberculosis [49], anti-diabetic and anti-bacterial properties [50].…”

mentioning

confidence: 97%

Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies

Rauf

Shahzad

Bajda

et al. 2015

Bioorganic & Medicinal Chemistry

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“…On the other hand, barbiturate derivatives also possess several biological activities such as anticancer [22], antiviral [23,24], sedative, hypnotic, antispasmodic, anticonvulsant, and local anesthesia [25], as well as antiinflammatory [26] activities. Prompted by the above facts and in continuation of our work on barbiturates [27,28], herein we report the synthesis of novel pyrimidine …”

Section: Introductionmentioning

confidence: 95%

Synthesis and antimicrobial activity of novel imidazo[1,2-a]pyridinopyrimidine-2,4,6(1H,3H,5H)-triones and thioxopyrimidine-4,6(1H,5H)diones

et al. 2015

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A novel series of imidazo[1,2-a]pyridinopyrimidine-2,4,6(1H,3H,5H)-triones and thioxopyrimidine-4,6(1H,5H)diones were synthesized via multistep synthesis starting from 2-aminopyridine on cyclisation with phenacyl bromide followed by Vilsmeier-Haack and Knoevenagel condensation reactions. Structures of all the newly synthesized compounds were confirmed by their spectral and analytical studies. All the synthesized compounds were screened for their in vitro antimicrobial activity. Antibacterial activity results revealed that compounds 5f, 5i, and 5j have shown promising activity against S. pyogenes with ZOI ranging from 19 to 20 mm, compound 5g against P. aeruginosa (ZOI 19 mm) and 5f and 5h against S. aureus (ZOI 17, 18 mm) have shown good antibacterial activity. Among barbituric acid and thiobarbituric acid derivatives, thiobarbituric acid derivatives have shown maximum antibacterial activity. None of the compounds were found to be active at 150 lg/mL concentration against tested fungal strains.

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“…The treatment of infection caused by ureolytic bacteria with antimicrobials, however, often proved to be unsuccessful [ 13 ]. The barbiturates possessed a wide range of pharmacological applications, such as anticonvulsant, sedative, anxiolytic, urease inhibition [ 18 ], antifungal [ 19 ], antimicrobial [ 20 , 21 ], antitumor, antiviral [ 13 , 22 ] anti tuberculosis [ 23 ], mushroom tyrosinase inhibition [ 24 ], radio-sensitization [ 25 ], anti-inflammatory, anticancer [ 26 ], anesthetic [ 27 ], diaminopimelate aminotransferase inhibition [ 28 ], and anti-proliferative activities [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors

Barakat

Al‐Majid

Lotfy

et al. 2015

Chemistry Central Journal

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BackgroundDiscovery of potent inhibitors of urease (jack bean) enzyme is the first step in the development of drugs against diseases caused by ureolytic enzyme.ResultsThirty-two derivatives of barbituric acid as zwitterionic adducts of diethyl ammonium salts were synthesized. All synthesized compounds (4a–z and 5a–s) were screened for their in vitro inhibition potential against urease enzyme (jack bean urease). The compounds 4i (IC50 = 17.6 ± 0.23 µM) and 5l (IC50 = 17.2 ± 0.44 µM) were found to be the most active members of the series, and showed several fold more urease inhibition activity than the standard compound thiourea (IC50 = 21.2 ± 1.3 µM). Whereas, compounds 4a–b, 4d–e, 4g–h, 4j–4r, 4x, 4z, 5b, 5e, 5k, 5n–5q having IC50 values in the range of 22.7 ± 0.20 µM–43.8 ± 0.33 µM, were also found as potent urease inhibitors. Furthermore, Molecular Dynamics simulation and molecular docking studies were carried out to analyze the binding mode of barbituric acid derivatives using MOE. During MD simulation enol form is found to be more stable over its keto form due to their coordination with catalytic Nickel ion of Urease. Additionally, structural–activity relationship using automated docking method was applied where the compounds with high biological activity are deeply buried within the binding pocket of urease. As multiple hydrophilic crucial interactions with Ala169, KCX219, Asp362 and Ala366 stabilize the compound within the binding site, thus contributing greater activity.ConclusionsThis research study is useful for the discovery of economically, efficient viable new drug against infectious diseases.Graphical abstract:STD. Thiourea (IC50 = 21.2 ± 1.3 µM)Electronic supplementary materialThe online version of this article (doi:10.1186/s13065-015-0140-1) contains supplementary material, which is available to authorized users.

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Synthesis and evaluation of chromenyl barbiturates and thiobarbiturates as potential antitubercular agents

Cited by 64 publications

References 10 publications

Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies

Design and synthesis of new barbituric- and thiobarbituric acid derivatives as potent urease inhibitors: Structure activity relationship and molecular modeling studies

Synthesis and antimicrobial activity of novel imidazo[1,2-a]pyridinopyrimidine-2,4,6(1H,3H,5H)-triones and thioxopyrimidine-4,6(1H,5H)diones

Synthesis and dynamics studies of barbituric acid derivatives as urease inhibitors

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