Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

Ramesh, Remya; Shingare, Rahul D.; Kumar, Vinod; Anand, Amitesh; Swetha, B.; Veeraraghavan, Sridhar; Viswanadha, Srikant; Ummanni, Ramesh; Gokhale, Rajesh S.; Reddy, D. Srinivasa

doi:10.1016/j.ejmech.2016.07.009

Cited by 65 publications

(36 citation statements)

References 33 publications

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“…Usually high PPB is associated with a lower clearance rate resulting in a greater half-time in vivo compared with low protein binding compounds. Despite the fact that drugs with low protein binding are believed to be more efficacious because of higher free drug concentration, there are studies concluding that the binding of a drug to plasma proteins has little effect on the in vivo efficacy of that drug 29 , 30 .…”

Section: Resultsmentioning

confidence: 99%

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12

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Danac

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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A series of 13 compounds having a monoindolizine mono-salt skeleton was designed and synthesised in order to evaluate their antimycobacterial activity. The synthesis is efficient, involving only three steps: two alkylations and one 3 + 2 dipolar cycloaddition. The antimicrobial activity against Mycobacterium tuberculosis H37Rv grown under aerobic conditions was evaluated, eight compounds showing a very good antimycobacterial activity. SAR correlation reveals a certain influence of the R substituent from the para position of benzoyl moiety at position 3 of indolizine. The most active five compounds passed the second stage of anti-TB testing, the assay demonstrating that they are potent against both replicating and non-replicating Mtb, have a bactericidal mechanism of action, are active against drug-resistant Mtb strains, present a moderate to good activity against nontuberculous mycobacteria, a good intracellular activity, and a moderate to high cytotoxicity. For one compound showing a promising anti-TB profile, a complete ADMET study has been performed.

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Section: Resultsmentioning

confidence: 99%

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12

Olaru

Vasilache

Danac

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…Among the synthesized compounds, derivatives 375 emerged as active anti-TB leads which exhibited low toxicity profile and high selectivity index value [ 274 ]. A novel sila analogues of Rimonabant as potent anti-tubercular agents were identified by Ramesh et al the sila analogue 376 was found to be the most potent anti-mycobacterial compound with MIC = 31 nM from this series with an excellent selectivity index [ 275 ]. Various 1-((1-(substituted)-1 H -1,2,3-triazol-4-yl) methyl)- N ,3-diphenyl-6,7-dihydro-1 H -pyrazolo[4,3- c ]pyridine-5(4 H )-carboxamides were prepared and screened for in vitro anti-tubercular activity against M. tuberculosis H37Rv strain.…”

Section: Pharmacological Activitiesmentioning

confidence: 99%

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

et al. 2018

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Pyrazole and its derivatives are considered a pharmacologically important active scaffold that possesses almost all types of pharmacological activities. The presence of this nucleus in pharmacological agents of diverse therapeutic categories such as celecoxib, a potent anti-inflammatory, the antipsychotic CDPPB, the anti-obesity drug rimonabant, difenamizole, an analgesic, betazole, a H2-receptor agonist and the antidepressant agent fezolamide have proved the pharmacological potential of the pyrazole moiety. Owing to this diversity in the biological field, this nucleus has attracted the attention of many researchers to study its skeleton chemically and biologically. This review highlights the different synthesis methods and the pharmacological properties of pyrazole derivatives. Studies on the synthesis and biological activity of pyrazole derivatives developed by many scientists around the globe are reported.

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“…Pyrazole and its derivatives are potent medicinal scaffolds, and they exhibit a large spectrum of biological activities against infectious diseases. They showed antibacterial and antifungal, antitubercular, anticancer, antioxidant, anti‐inflammatory and antipyretic activities. Quinoline tethered azole hybrids are important pharmacophores that possess a wide range of biological activities .…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Biological Evaluation of New 1,2,3‐Triazolyl‐Pyrazolyl‐Quinoline Derivatives as Potential Antimicrobial Agents

et al. 2020

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A new series of 4-{1-phenyl-4-[(4-phenyl-1,2,3-triazol-1-yl)methyl]pyrazol-3-yl}quinoline (7a-l) have been synthesized by a click reaction of 4-(4-(azidomethyl)-1-phenyl-1H-pyrazol-3-yl) quinoline (5a-d) with a substituted ethynylbenzene. The newly synthesized 1,2,3-triazolyl-pyrazolyl-quinoline derivatives were evaluated for biological activity against Escherichia coli (NCIM 2574), Proteus mirabilis (NCIM 2388), (Gram negative strains), Bacillus subtilis (NCIM 2063), Staphylococcus albus (NCIM 2178) (Gram positive strains) and in vitro antifungal activity against Candida albicans (NCIM 3100) and Aspergillus niger (ATCC 504). Five 1,2,3-triazolyl-pyrazolyl-quinoline derivatives, 7d, 7 g, 7 h, 7k and 7 l exhibited good antifungal activity against A. niger with MIC 62.5 μg/mL. The compounds 7 h, 7k and 7 l were further evaluated for ergosterol inhibition assay against A. niger cell sample at 62.5 μg/mL concentration. Upon analysis of the sterol inhibition assay, it was revealed that, the ergosterol biosynthesis has decreased in the fungal samples treated with the 1,2,3-triazolyl-pyrazolyl-quinoline derivatives. Thus antimicrobial activity suggested that, these compounds could aid and assist in the development of lead compounds to treat microbial infections.

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Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

Cited by 65 publications

References 33 publications

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Biological Evaluation of New 1,2,3‐Triazolyl‐Pyrazolyl‐Quinoline Derivatives as Potential Antimicrobial Agents

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Repurposing of a drug scaffold: Identification of novel sila analogues of rimonabant as potent antitubercular agents

Cited by 65 publications

References 33 publications

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII8–12

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII8–12

Synthesis and Pharmacological Activities of Pyrazole Derivatives: A Review

Synthesis and Biological Evaluation of New 1,2,3‐Triazolyl‐Pyrazolyl‐Quinoline Derivatives as Potential Antimicrobial Agents

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Product

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Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12

Antimycobacterial activity of nitrogen heterocycles derivatives: 7-(pyridine-4-yl)-indolizine derivatives. Part VII^8–12