Design and synthesis of novel pyrimidine derivatives as potent antitubercular agents

Liu, Pingxian; Yang, Yang; Tang, Yue-Hua; Yang, Tao; Sang, Zitai; Li, Yong; Zhang, Tianyu; Luo, Youfu

doi:10.1016/j.ejmech.2018.11.054

Cited by 62 publications

(26 citation statements)

References 18 publications

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“…Ceritinib analogue 91 (Figure ) was reported by Liu et al as a putative DHFR inhibitor with moderate anti-TB activity . The original HTS hit, ceritinib ( 90 ) (Figure ), an anaplastic lymphoma kinase inhibitor approved for use against lung cancer (NSCLC), was modestly active against autoluminescent Mtb H37Ra (MIC 90 9.0 μM).…”

Section: Preclinical Promisesmentioning

confidence: 99%

Tuberculosis Drug Discovery: Challenges and New Horizons

et al. 2022

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Over the past 2000 years, tuberculosis (TB) has claimed more lives than any other infectious disease. In 2020 alone, TB was responsible for 1.5 million deaths worldwide, comparable to the 1.8 million deaths caused by COVID-19. The World Health Organization has stated that new TB drugs must be developed to end this pandemic. After decades of neglect in this field, a renaissance era of TB drug discovery has arrived, in which many novel candidates have entered clinical trials. However, while hundreds of molecules are reported annually as promising anti-TB agents, very few successfully progress to clinical development. In this Perspective, we critically review those anti-TB compounds published in the last 6 years that demonstrate good in vivo efficacy against Mycobacterium tuberculosis. Additionally, we highlight the main challenges and strategies for developing new TB drugs and the current global pipeline of drug candidates in clinical studies to foment fresh research perspectives.

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Section: Preclinical Promisesmentioning

confidence: 99%

Tuberculosis Drug Discovery: Challenges and New Horizons

et al. 2022

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“…Cucumerinum , the causative agent driving cucumber fusarium wilt disease; we measured an IC 50 value of 6.99 μM, which is more effective than the positive control, cycloheximide (8.17 μM). We also evaluated compounds 1 and 2 for antitubercular activities against M. tuberculosis H37Rv using rifampicin (MIC = 0.25 μg mL –1 ) as a positive control. The MICs of both 1 and 2 were 2.5 μg mL –1 .…”

mentioning

confidence: 99%

Discovery and Biosynthesis of Atrovimycin, an Antitubercular and Antifungal Cyclodepsipeptide Featuring Vicinal-dihydroxylated Cinnamic Acyl Chain

Liu

Sun

et al. 2019

Org. Lett.

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Atrovimycin (1), a cyclodepsipeptide containing a unique vicinal-hydroxylated cinnamic acyl chain, was isolated and elucidated from Streptomyces atrovirens LQ13. The biosynthetic pathway of 1 was achieved, revealing cytochrome P450 (Avm43) and epoxide hydrolase (Avm29) enzymes constructing the vicinal-dihydroxy substitution, as well as a tailoring P450 (Avm28) enzyme catalyzing β-hydroxylation of the l-Phe moiety. Atrovimycin shows in vitro antifungal activity and antitubercular activity against Mycobacterium tuberculosis H37Rv both in vitro (with MIC of 2.5 μg/mL) and in vivo.

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“…64,65 The inclusion of TB47 or its derivatives to the current drug regimen may have desirable outcomes in the pursuit of multi-target approaches of various complex diseases. 65,66 Bacteriophages or phages are viruses that infect and lyse specific bacterial cells. 67 Phage-treatment against bacterial infections was first used in the early 1920s; however, subsequently lost favour due to the discovery of antibiotics.…”

Section: Mycobacterium Tuberculosis Drug Development and Phage-based Therapy: Potential Anti-tb Treatmentmentioning

confidence: 99%

<p>Potential Impact of the Multi-Target Drug Approach in the Treatment of Some Complex Diseases</p>

Makhoba¹,

Viegas²,

Mosa³

et al. 2020

DDDT

168

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It is essential to acknowledge the efforts made thus far to manage or eliminate various disease burden faced by humankind. However, the rising global trends of the so-called incurable diseases continue to put pressure on Pharma industries and other drug discovery platforms. In the past, drugs with more than one target were deemed as undesirable options with interest being on the one-drug-single target. Despite the successes of the single-target drugs, it is currently beyond doubt that these drugs have limited efficacy against complex diseases in which the pathogenesis is dependent on a set of biochemical events and several bioreceptors operating concomitantly. Different approaches have thus been proposed to come up with effective drugs to combat even the complex diseases. In the past, the focus was on producing drugs from screening plant compounds; today, we talk about combination therapy and multi-targeting drugs. The multi-target drugs have recently attracted much attention as promising tools to fight against most challenging diseases, and thus a new research focus area. This review will discuss the potential impact of multi-target drug approach on various complex diseases with focus on malaria, tuberculosis (TB), diabetes and neurodegenerative diseases as the main representatives of multifactorial diseases. We will also discuss alternative ideas to solve the current problems bearing in mind the fourth industrial revolution on drug discovery.

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Design and synthesis of novel pyrimidine derivatives as potent antitubercular agents

Cited by 62 publications

References 18 publications

Tuberculosis Drug Discovery: Challenges and New Horizons

Tuberculosis Drug Discovery: Challenges and New Horizons

Discovery and Biosynthesis of Atrovimycin, an Antitubercular and Antifungal Cyclodepsipeptide Featuring Vicinal-dihydroxylated Cinnamic Acyl Chain

<p>Potential Impact of the Multi-Target Drug Approach in the Treatment of Some Complex Diseases</p>

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