Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase

Patel, Bhargav A.; Krishnan, Ramalingam; Khadtare, Nikhil; Gurukumar, K.R.; Basu, Amartya; Arora, Payal; Bhatt, Aaditya; Patel, Maulik; Dana, Dibyendu; Kumar, Shiv Datt; Kaushik‐Basu, Neerja; Talele, Tanaji T.

doi:10.1016/j.bmc.2013.03.041

Cited by 18 publications

(10 citation statements)

References 32 publications

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“…The antiviral N-acylpyrolidine library (92 & 93) afforded clinical candidate (94) against HCV infections were discovered by HTS screening. The HTS assay against HCV NS5B polymerase identified a series of rhodanine analogues (95, 96 and 96e1) as promising antiviral agents and optimized by having chloro substitutions as essential for efficiency [71]. The benzodiazepine antipsychotic scaffold (97 to 99) targeting NS5B polymerase was scrutinized via SBBD platform and experimented as anti-HCV agents.…”

Section: Nucleoside Non-nucleoside and Protease Inhibitors As Anti-hmentioning

confidence: 99%

A review on HCV inhibitors: Significance of non-structural polyproteins

Ganta¹,

Gedda

Rathnakar

et al. 2019

European Journal of Medicinal Chemistry

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a b s t r a c tHepatitis C virus (HCV) mortality and morbidity is a world health misery with an approximate 130e150 million chronically HCV tainted and suffering individuals and it initiate critical liver malfunction like cirrhosis, hepatocellular carcinoma or liver HCV cancer. HCV NS5B protein one of the best studied therapeutic target for the identification of new drug candidates to be added to the combination or multiple combination medication recently approved. During the past few years, NS5B has thus been an important object of attractive medicinal chemistry endeavors, which induced to the surfacing of betrothal preclinical drug molecules. In this scenario, the current review set limit to discuss research published on NS5B and few other therapeutic functional inhibitors concentrating on hit investigation, hit to lead optimization, ADME parameters evaluation, and the SAR data which was out for each compound type and similarity taken into consideration. The discussion outlined in this specific review will surly helpful and vital tool for those medicinal chemists investigators working with HCV research programs mainly pointing on NS5B and set broad spectrum identification of creative anti HCV compounds. This mini review also tells each and every individual compound ability related how much they are active against NS5B and few other targets.

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Section: Nucleoside Non-nucleoside and Protease Inhibitors As Anti-hmentioning

confidence: 99%

A review on HCV inhibitors: Significance of non-structural polyproteins

Ganta¹,

Gedda

Rathnakar

et al. 2019

European Journal of Medicinal Chemistry

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“…The syntheses of compounds 1 and 4 – 6 [ 3 ] and 2 , 3 and 7 [ 1 ] was previously reported by our group and that for compounds 8 – 10 is reported herein (see Supporting Information ). LogP and LogS were predicted for all the compounds to assess their lipophilicity and water solubility using QikProp, version 4.8, Schrödinger, LLC, NY.…”

Section: Methodsmentioning

confidence: 92%

“…Recently, we synthesized compounds known as rhodanines and determined their efficacy in vitro against various MRSA strains [ 1 , 3 ]. Our results indicated that certain rhodanine derivatives were efficacious against six clinically relevant MRSA strains [ 1 ].…”

Section: Discussionmentioning

confidence: 99%

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

et al. 2016

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Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives have been shown to possess potent antimicrobial activity via a novel mechanism. However, their potential use as antibacterials has not been fully examined. In this study, we determined the spectrum of activity of seven rhodanine derivatives (compounds Rh 1–7) against clinical isolates of Gram-positive and Gram-negative bacterial strains and Candida albicans. We also synthesized and tested three additional compounds, ethyl ester and amide of rhodanine 2 (Rh 8 and Rh 10, respectively) and ethyl ester of rhodanine 3 (Rh 9) to determine the significance of the carboxyl group modification towards antibacterial activity and human serum albumin binding. A broth microdilution assay confirmed Rh 1–7 exhibit bactericidal activity against Gram-positive pathogens. Rh 2 had significant activity against various vancomycin-resistant (MIC90 = 4 μM) and methicillin-resistant (MIC90 = 4 μM) Staphylococcus aureus (VRSA and MRSA), Staphylococcus epidermidis (MIC = 4 μM) and vancomycin-resistant Enterococcus (VRE) strains (MIC90 = 8 μM). The rhodanine compounds exhibited potent activity against Bacillus spp., including Bacillus anthracis, with MIC range of 2–8 μM. In addition, they had potent activity against Clostridium difficile. The most potent compound, Rh 2, at 4 and 8 times its MIC, significantly decreased S. epidermidis biofilm mass by more than 35% and 45%, respectively. None of the rhodanine compounds showed antimicrobial activity (MIC > 128 μM) against various 1) Gram-negative pathogens (Acinetobacter baumannii, Escherichia coli, Klebsiella pneumonia, Pseudomonas aeruginosa, and Salmonella Typhimurium) or 2) strains of Candida albicans (MIC > 64 μM). The MTS assay confirmed that rhodanines were not toxic to mouse murine macrophage (J774.1A) up to 64 μM, human keratinocytes (HaCat) up to 32 μM, and human ileocecal colorectal cell (HRT-18) up to 128 μM. Overall, these data suggest that certain rhodanine compounds may have potential use for the treatment of several multidrug-resistant Gram-positive bacterial infections.

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“…Patel et al [40] have reported the synthesis and in vitro evaluation of anti-NS5B polymerase activity of some novel rhodanine derivatives. Depending on the nature of substituents, the tested compounds exhibited IC 50 values ranging between 2 and 50 µM against NS5B polymerase.…”

Section: (Xxxvi)mentioning

confidence: 99%

Recent Advances in the Biological Importance of Rhodanine Derivatives

Patel¹,

Kumari²

2016

Scope of Selective Heterocycles From Organic and Pharmaceutical Perspective

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Heterocyclic compounds are an important part of the synthetic medicinal chemistry. They offer a high degree of structural variety and have proven to be widely useful as therapeutic agents. Heterocyclic compounds play an important role in the biological processes. They are widespread as natural products. Heterocyclic compounds are widely found in nature categorically in plant alkaloids, nucleic acids, anthocyanins, and flavones. They are also present as in chlorophyll and hemoglobin. "dditionally, some proteins, hormones, and vitamins also contain aromatic heterocyclic system. Heterocycles have huge potential as the most promising molecules as lead structures for the design of new drugs. "bout one half of over million compounds recorded so far in chemical abstracts are heterocyclic. The proposed book chapter entitled, Recent Advances in the Biological Importance of Rhodanine Derivatives gives an outline of importance and applications of the various rhodanine derivatives in medicinal chemistry from to .

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Design and synthesis of l- and d-phenylalanine derived rhodanines with novel C5-arylidenes as inhibitors of HCV NS5B polymerase

Cited by 18 publications

References 32 publications

A review on HCV inhibitors: Significance of non-structural polyproteins

A review on HCV inhibitors: Significance of non-structural polyproteins

In Vitro Antibacterial Activity of Rhodanine Derivatives against Pathogenic Clinical Isolates

Recent Advances in the Biological Importance of Rhodanine Derivatives

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