9-Benzylpurines with inhibitory activity against Mycobacterium tuberculosis

Bakkestuen, Anne Kristin; Gundersen, Lise‐Lotte; Langli, Geir; Liu, Fusheng; Nolsöe, Jens M. J.

doi:10.1016/s0960-894x(00)00188-8

Cited by 124 publications

(64 citation statements)

References 10 publications

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“…Compound (4) was then condensed with various freshly synthesized 2-bromo-1-(substituted phenyl)-ethanones (5a−5o) to yield corresponding final compounds, i.e., 2-(2-((2E,3E)-4-(3,4-dimethoxyphenyl)-but-3-en-2-ylidene)hydrazinyl)-4-(substituted phenyl)thiazoles (6a−6o; Scheme 2). The anticipated structures of the final compounds were in agreement with the spectral (IR, 1 H NMR, and 13 C NMR) data obtained and were further substantiated by …”

supporting

confidence: 80%

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Hampannavar

Karpoormath

Palkar

et al. 2016

ACS Med. Chem. Lett.

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Series of styryl hydrazine thiazole hybrids inspired from dehydrozingerone (DZG) scaffold were designed and synthesized by molecular hybridization approach. In vitro antimycobacterial activity of synthesized compounds was evaluated against Mycobacterium tuberculosis H 37 Rv strain. Among the series, compound 6o exhibited significant activity (MIC = 1.5 μM; IC 50 = 0.48 μM) along with bactericidal (MBC = 12 μM) and intracellular antimycobacterial activities (IC 50 = <0.098 μM). Furthermore, 6o displayed prominent antimycobacterial activity under hypoxic (MIC = 46 μM) and normal oxygen (MIC = 0.28 μM) conditions along with antimycobacterial efficiency against isoniazid (MIC = 3.2 μM for INH-R1; 1.5 μM for INH-R2) and rifampicin (MIC = 2.2 μM for RIF-R1; 6.3 μM for RIF-R2) resistant strains of Mtb. Presence of electron donating groups on the phenyl ring of thiazole moiety had positive correlation for biological activity, suggesting the importance of molecular hybridization approach for the development of newer DZG clubbed hydrazine thiazole hybrids as potential antimycobacterial agents. KEYWORDS: Antimycobacterial activity, bactericidal, dehydrozingerone, NIAID, thiazole T uberculosis (TB) is a chronic necrotizing bacterial infection caused by Mycobacterium tuberculosis (Mtb), which has been a bane of humanity for thousands of years and remains as one of the rampant health problems in the world. TB is an ancient enemy, and current threat that has been ranked among the foremost killers of the 21st century. 1According to a World Health Organization (WHO) report, around 9 million people were found infected and around 1.5 million casualties occurred because of TB. Besides, the life threatening strains of MDR-TB (Multi Drug Resistance Tuberculosis) are appearing, some of which can lead to high mortality rate (e.g., 72−89%) with death occurring in short period (4−16 weeks).2 In 2013 around 480,000 affirmative cases of MDR-TB were witnessed.3 India, China, the Russian Federation, and South Africa have almost 60% of the world's cases of MDR-TB. In addition, the risk becomes even greater if the person is coinfected with the HIV (human immunodeficiency virus). 4 The global resurgence of TB and development of drug resistance necessitates for an imperative attention of medicinal chemists to develop innovative antimycobacterial agents as no new classes of anti-TB agents have been developed since the introduction of rifampin in to clinical practice in 1960s.It is well-known fact that trans-cinnamic acid analogues have recently drawn back the intentness of medicinal chemists due to their admirable pharmacological properties like antioxidant,

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supporting

confidence: 80%

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Hampannavar

Karpoormath

Palkar

et al. 2016

ACS Med. Chem. Lett.

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“…High activity was exhibited by 9-benzylpurines carrying a phenyl ethynyl, transstyryl or aryl substituents at the 6 th position and generally chlorine at the 2 nd position. The most active compounds 46 showed a MIC of 3.13 and 0.78 μg/mL respectively, against Mtb H37Rv and also a selectivity index (SI) of 2.7 and 10.4 [67]. In continuation, a series of 6-arylpurines having a variety of substituents in the 9 position and were screened against Mtb H37Rv [68].…”

Section: A Series Of N-phenyl-6-methyl-2-oxo-4-phenyl-1234-tetrahydromentioning

confidence: 99%

Recent Efforts for the Development of Antitubercular Drug Containing Diazine Ring

Asif¹

2012

Med chem

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There has been considerable interest in the development of new molecule with antibacterial activities particularly against tuberclosis because mycobacterium species have developed resistant against currently used drugs, their toxic effect and long duration of therapy. The diazine (pyridazine, pyrimidine and piperazine) derivatives possess an important class of compound for new drugs research and development. Therefore, many researchers have synthesized these compounds as target structures and evaluated their antitubercular activity. These observations have been guiding for the development of new molecules that possess potent antitubercular activity with minimum side effects or effective against MDR, XDR mycobacterium strains, and also in patient co-infected with HIV/AIDS.

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“…Structure-activity relationship studies have shown that the nitro group is necessary for biological activity. One of the compounds, 39 belonging to the above class carrying trans-styryl or aryl substituents at 6 position and generally chlorine in 2 position tends to increase the activity and has MIC of 0.78 mg/mL in vitro (77). Antimycobacterial activity of 6-arylpurines (78) and 9-sulphonylated or sulphenylated-6-mercaptopurines are also known in the literature (79).…”

Section: Nitrofuranyl Amidesmentioning

confidence: 99%

Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds

et al. 2008

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Development of new chemotherapeutic drugs is the need of the hour to improve tuberculosis control, particularly in the developing world. In the last fourty years no new compound has been brought to the market for the treatment of tuberculosis. However, in recent years there is an enhanced activity in the research and development of new drugs for TB. Some compounds are presently in clinical development, while others are being investigated pre-clinically in an attempt to explore new molecules for the target based treatment of TB. Simultaneously some new targets are being identified and validated for their practical usefulness. Structures based on thiolactomycin could have considerable potential in the development of target based anti-TB agents. The present review provides an overview of the drugs that are being clinically used and the compounds that are in advanced stages of clinical as well as preclinical studies. We have also attempted to highlight the efforts that are being made in the development of new molecules based on thiolactomycin as lead compound, including studies from this laboratory.

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9-Benzylpurines with inhibitory activity against Mycobacterium tuberculosis

Cited by 124 publications

References 10 publications

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Dehydrozingerone Inspired Styryl Hydrazine Thiazole Hybrids as Promising Class of Antimycobacterial Agents

Recent Efforts for the Development of Antitubercular Drug Containing Diazine Ring

Efforts Towards the Development of New Antitubercular Agents: Potential for Thiolactomycin Based Compounds

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