Triazole-containing hybrids with anti-Mycobacterium tuberculosis potential – Part I: 1,2,3-Triazole

2021 ◽  
Author(s):  
Zhenyou Tan ◽  
Jun Deng ◽  
Qiongxian Ye ◽  
Zhenfeng Zhang
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Rational Design ◽  
Multidrug Therapy ◽  
Resistance Development ◽  
Drug Candidates ◽  
Structure Activity ◽  
Privileged Structure ◽  
Potential Part ◽  
Potential Activity

Tuberculosis regimens currently applied in clinical practice require months of multidrug therapy, which imposes a major challenge of patient compliance and drug resistance development. Moreover, because of the increasing emergence of hard-to-treat tuberculosis, this disease continues to be a significant threat to the human population. 1,2,3-triazole as a privileged structure has been widely used as an effective template for drug discovery, and 1,2,3-triazole-containing hybrids that can simultaneously act on dual or multiple targets in Mycobacterium tuberculosis have the potential to circumvent drug resistance, enhance efficacy, reduce side effects and improve pharmacokinetic as well as pharmacodynamic profiles. Thus, 1,2,3-triazole-containing hybrids are useful scaffolds for the development of antitubercular agents. This review aims to highlight recent advances of 1,2,3-triazole-containing hybrids with potential activity against various forms of M. tuberculosis, covering articles published between 2015 and 2020. The structure–activity relationship and the mechanism of action are also discussed to facilitate further rational design of more effective drug candidates.

Current insights into the chemistry and antitubercular potential of benzimidazole and imidazole derivatives

2020 ◽  
Vol 20 ◽  
Author(s):  
Deepa Parwani ◽  
Sushanta Bhattacharya ◽  
Akash Rathore ◽  
Chaitali Mallick ◽  
Vivek Asati ◽  
...  
Keyword(s):  
Drug Resistance ◽  
Mycobacterium Tuberculosis ◽  
Multi Drug Resistance ◽  
Benzimidazole Derivatives ◽  
Duration Of Treatment ◽  
Structure Activity ◽  
Mdr Tb ◽  
Low Toxicity ◽  
Extensively Drug Resistance ◽  
Improved Characteristics

: Tuberculosis is a disease caused by Mycobacterium tuberculosis (Mtb), affecting millions of people worldwide. The emergence of drug resistance is a major problem in the successful treatment of tuberculosis. Due to the commencement of MDR-TB (multi-drug resistance) and XDR-TB (extensively drug resistance), there is a crucial need for the development of novel anti-tubercular agents with improved characteristics such as low toxicity, enhanced inhibitory activity and short duration of treatment. In this direction, various heterocyclic compounds have been synthesized and screened against Mycobacterium tuberculosis. Among them, benzimidazole and imidazole containing derivatives found to have potential anti-tubercular activity. The present review focuses on various imidazole and benzimidazole derivatives (from 2015-2019) with their structure activity relationships in the treatment of tuberculosis.

Pharmacologic activities of 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4-triazines as a privileged scaffold in drug development

2021 ◽  
Vol 21 ◽  
Author(s):  
Zahra Zakeri Khatir ◽  
Hamid Irannejad
Keyword(s):  
Biological Data ◽  
Pharmacological Activities ◽  
Drug Candidates ◽  
Structure Activity ◽  
Wide Range ◽  
Privileged Structure ◽  
Triazine Derivatives ◽  
Privileged Scaffold ◽  
Substituted 1 ◽  
Anti Hiv

: 1, 2, 4-Triazine derivatives have received much attention due to their multifunctional nature, especially in diverse pharmacological properties as well as a key fragment in many drug candidates. Introduction of a vicinal 5, 6-diaryl/heteroaryl moiety on the 1, 2, 4-triazine ring has attracted plentiful attention in the field of medicinal chemistry. 5, 6-Diaryl/heteroaryl-3-substituted-1, 2, 4-triazine is as a prominent scaffold in many drug candidates which has shown a wide range of pharmacological activities such as anti-diabetic, antifungal, anti-inflammatory, anticancer, anti-HIV, neuroprotective, anticonvulsant, anti- Alzheimer, anti-Parkinson and antioxidant. In this review, we have discussed synthesis, various pharmacological activities of 5, 6-diaryl/heteroaryl-3-substituted-1, 2, 4-triazines, their structure-activity relationship (SAR), pharmacophoric elements and their mechanism of action reported in the published articles during 2000-2019. Evaluation of compounds by PAINS filtering tool was accomplished and showed that this versatile structure could be considered as a privileged structure. Compilation of the biological data confirmed that the position 3 of the 1,2,4-triazine is a key location to determine the affinity and selectivity of the 5,6-diaryl/heteroaryl-3-substituted-1, 2, 4-triazines towards different biologic targets. Specific geometrical and thermodynamic characters of this motif have prompted it as a frequent hitter.

Chalcone derivatives and their activities against drug-resistant cancers: An overview

2020 ◽  
Vol 20 ◽  
Author(s):  
Jiaqi Xiao ◽  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao
Keyword(s):  
Drug Resistance ◽  
Multidrug Resistance ◽  
Cancer Cells ◽  
Anticancer Agents ◽  
Rational Design ◽  
Multidrug Resistant ◽  
Drug Resistant ◽  
Chalcone Derivatives ◽  
Potential Activity ◽  
Defensive Mechanisms

: Drug resistance including multidrug resistance resulting from different defensive mechanisms in cancer cells is the leading cause of the failure about the cancer therapy, making it an urgent need to develop more effective anticancer agents. Chalcones, widely distributed in nature, could act on diverse enzymes and receptors in cancer cells. Accordingly, chalcone derivatives possess potential activity against various cancers including drug-resistant even multidrug-resistant cancer. This review outlines the recent development of chalcone derivatives with potential activity against drug-resistant cancers covering articles published between 2010 and 2020, so as to facilitate further rational design of more effective candidate.

Current scenario of acridine hybrids with anticancer potential

2021 ◽  
Vol 21 ◽  
Author(s):  
Qihong Zhang ◽  
Xia Yu
Keyword(s):  
Anticancer Activity ◽  
Anticancer Agents ◽  
Rational Design ◽  
Complex Disease ◽  
Single Agent ◽  
Drug Candidates ◽  
Cycle Arrest ◽  
Current Scenario ◽  
Potential Activity ◽  
Almost All

: Cancer, a complex disease which involves abnormalities of multiple cellular pathways, is one of the most serious threatens to human health across the world. Chemotherapy with a single agent or a combined regimen is a standardized strategy for the treatment of almost all human cancers, and the cure rate of cancer increases with the continuous discovery of anticancer agents and the optimization of chemotherapy options. However, drug resistance especially multidrug resistance remains an obstacle in the effective treatment of cancer. Hence, it is urgent to develop novel agents with potential activity against cancers, especially drug-resistant forms. Acridine, which bears three fused rings, could intercalate into DNA and interfere with metabolic processes. Recently, acridines have been found with anticancer activity in a variety of malignancies through suppressing cell proliferation, stimulating apoptosis, and inducing cell cycle arrest, retarding migration, invasion and metastasis. Thus, acridines are useful scaffolds for the discovery of novel drug candidates with potent anticancer activity. This review focused on the current scenario of acridine hybrids with potential activity against cancers reported from Jan. 2015 to Feb. 2021. The mechanisms of action, the criteria of compound design as well as structure-activity relationships were also summarized to pave the way for further rational design of novel anticancer agents.

Design of Novel Phosphopantetheine Adenylyltransferase Inhibitors: a Potential New Approach to Tackle Mycobacterium tuberculosis

2021 ◽  
Vol 21 ◽  
Author(s):  
Marina C. Primi ◽  
Maurício T. Tavares ◽  
Larry L. Klein ◽  
Tina Izard ◽  
Carlos M. R. Sant'Anna ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Drug Design ◽  
Rational Design ◽  
Multi Drug Resistance ◽  
Design Strategies ◽  
Structure Based Drug Design ◽  
New Approach ◽  
Docking Simulations ◽  
Structure Activity ◽  
The World

Background: Tuberculosis (TB) has been a challenging disease worldwide, especially for the neglected poor populations. Presently, there are approximately 2 billion people infected with TB worldwide and 10 million people in the world fell ill with active TB, leading to 1.5 million deaths. Introduction: The classic treatment is extensive and the drug and multi drug resistance of Mycobacterium tuberculosis has been a threat to the efficacy of the drugs currently used. Therefore, the rational design of new anti TB candidates is urgently needed. Methods: With the aim of contributing to face this challenge, 78 compounds have been proposed based on SBDD (Structure Based Drug Design) strategies applied to target the M. tuberculosis phosphopantetheine adenylyltransferase (MtPPAT) enzyme. Ligand Based Drug Design (LBDD) strategies were also used for establishing structure activity relationships (SAR) and for optimizing the structures. MtPPAT is important for the biosynthesis of coenzyme A (CoA) and it has been studied recently toward the discovery of new inhibitors. Results : After docking simulations and enthalpy calculations, the interaction of selected compounds with MtPPAT was found to be energetically favorable. The most promising compounds were then synthesized and submitted to anti M. tuberculosis and MtPPAT inhibition assays. Conclusion: One of the compounds synthesized (MCP163), showed the highest activity in both of these assays.

Synthesis and SAR Study of Simple Aryl Oximes and Nitrofuranyl Derivatives with Potent Activity Against Mycobacterium tuberculosis

2019 ◽  
Vol 17 (1) ◽  
pp. 12-20
Author(s):  
Cristiane França da Costa ◽  
Marcus Vinicius Nora de Souza ◽  
Maria Cristina da Silva Lourenço ◽  
Elaine Soares Coimbra ◽  
Guilherme da Silva Lourenço Carvalho ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Pseudomonas Aeruginosa ◽  
Mycobacterium Tuberculosis ◽  
Rational Design ◽  
Biological Activities ◽  
Shigella Flexneri ◽  
Selectivity Index ◽  
Mycobacterium Tuberculosis H37rv ◽  
Structure Activity ◽  
Sar Study

Background: Oximes and nitrofuranyl derivatives are particularly important compounds in medicinal chemistry. Thus, many researchers have been reported to possess antibacterial, antiparasitic, insecticidal and fungicidal activities. Methods: In this work, we report the synthesis and the biological activity against Mycobacterium tuberculosis H37RV of a series of fifty aryl oximes, ArCH=N-OH, I, and eight nitrofuranyl compounds, 2-nitrofuranyl-X, II. Results: Among the oximes, I: Ar = 2-OH-4-OH, 42, and I: Ar = 5-nitrofuranyl, 46, possessed the best activity at 3.74 and 32.0 µM, respectively. Also, 46, the nitrofuran compounds, II; X = MeO, 55, and II: X = NHCH2Ph, 58, (14.6 and 12.6 µM, respectively), exhibited excellent biological activities and were non-cytotoxic. Conclusion: The compound 55 showed a selectivity index of 9.85. Further antibacterial tests were performed with compound 55 which was inactive against Enterococcus faecalis, Klebisiella pneumonae, Pseudomonas aeruginosa, Staphylococcus aureus, Salmonella typhymurium and Shigella flexneri. This study adds important information to the rational design of new lead anti-TB drugs. Structure-activity Relationship (SAR) is reported.

Advances in the application of 1,2,4-triazole-containing hybrids as anti-tuberculosis agents

2021 ◽  
Author(s):  
Yingdong Cao ◽  
Hong Lu
Keyword(s):  
Side Effects ◽  
Rational Design ◽  
Communicable Disease ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Current Status ◽  
Potential Drug ◽  
Antitubercular Agents ◽  
Drug Candidates ◽  
Privileged Structure

Tuberculosis is a deadly communicable disease caused by the bacillus Mycobacterium tuberculosis (MTB), and pulmonary tuberculosis accounts for over 80% of the total cases. The 1,2,4-triazole is a privileged structure in the discovery of new drugs, and its derivatives act on various targets in MTB. In particular, 1,2,4-triazole hybrids can not only exert dual or multiple antitubercular mechanisms of action but also have the potential to enhance efficacy and reduce side effects. The present work aims to summarize the current status of 1,2,4-triazole hybrids as potential antitubercular agents, covering articles published between 2010 and 2020, to aid the further rational design of novel potential drug candidates endowed with higher efficacy, better compliance and fewer side effects.

Bis-triazole-containing compounds with anticancer potential: A short review

2021 ◽  
Vol 21 ◽  
Author(s):  
Meixiang Gao ◽  
Qiang Diao ◽  
Feng Gao ◽  
Xiangyang Sun ◽  
Jiaqi Xiao
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
High Efficiency ◽  
Short Review ◽  
Tumor Proliferation ◽  
Invasion And Metastasis ◽  
Drug Candidates ◽  
Structure Activity ◽  
Set Up ◽  
Biological Spectrum

: The development of novel anticancer agents with high efficiency is of great importance due to the severe anticancer scenario of the currently used drugs. Dimerization is a useful method to develop new drug candidates with a broad biological spectrum, enhanced activity and potency to overcome drug resistance. A wide variety of bis-triazole-containing compounds have been developed with improved properties compared with their parent compounds. These derivatives could inhibit tumor proliferation, invasion and metastasis, revealing their potential as putative anticancer candidates. This review covers the recent advances of bis-triazole-containing compounds as anticancer candidates, and the structure-activity relationship are also discussed to set up the direction for the design and development of bis-triazole-containing compounds with higher efficiency.

Quinoline-based compounds with potential activity against drug-resistant cancers

2020 ◽  
Vol 20 ◽  
Author(s):  
Huan-Ting Li ◽  
Xiaoyong Zhu
Keyword(s):  
Drug Resistance ◽  
Anticancer Agents ◽  
Anticancer Agent ◽  
Short Review ◽  
Therapeutic Strategies ◽  
Mechanisms Of Action ◽  
Review Article ◽  
Drug Resistant ◽  
Structure Activity ◽  
Potential Activity

: Drug resistance is the major cause of the failure of cancer chemotherapy, so one of the most important features in developing effective cancer therapeutic strategies is to overcome drug resistance. Quinoline moiety has become one of the most privileged structural motifs in anticancer agent discovery since its derivatives possess potential activity against various cancers including drug-resistant cancers. Several quinoline-based compounds which are represented by Anlotinib, Bosutinib, Lenvatinib, and Neratinib have already been applied in clinical practice to fight against cancers, so quinoline-based compounds are potential anticancer agents. The present short review article provides an overview about the recent advances of quinoline-based compounds with potential activity against drug-resistant cancers. The structure-activity relationship and mechanisms of action are also discussed.

Aminoglycosides with anti-MRSA activity: A concise review

2021 ◽  
Vol 21 ◽  
Author(s):  
Cheng-Jiao Yao ◽  
Yi-lin Li ◽  
Meng-Jun Pu ◽  
Li-Hong Luo ◽  
Qin Xiong ◽  
...  
Keyword(s):  
Rational Design ◽  
Multidrug Resistant ◽  
Medical Field ◽  
Drug Candidates ◽  
Concise Review ◽  
Current Scenario ◽  
Potential Activity ◽  
Gram Negative Organisms ◽  
Systemic Infections ◽  
Significant Health

: Methicillin-resistant Staphylococcus aureus (MRSA), a leading cause of infections in human being and is usually associated with a multidrug-resistant profile, represents a significant health threat and public burden globally. The limited options of effective antibiotics motivate the search for novel anti-MRSA agents. Aminoglycoside antibiotics have been extensively applied in the medical field due to their desirable broad-spectrum antibacterial activity, especially for systemic infections caused by Gram-negative organisms. Recent studies demonstrated that aminoglycosides also possessed potential activity against MRSA, so aminoglycosides may be useful weapons to fight against MRSA. The present work aims to summarize the current scenario of aminoglycosides with anti-MRSA potential, covering articles published between 2010 and 2020. The structure-activity relationship and the mechanism of action are also discussed for the further rational design of novel potential drug candidates.

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