Design and synthesis of β-amino alcohol based β-lactam–isatin chimeras and preliminary analysis of in vitro activity against the protozoal pathogen Trichomonas vaginalis

Nisha, .; Mehra, Vishu; Hopper, Melissa; Patel, Neal M.; Hall, Dominique; Wrischnik, Lisa A.; Land, Kirkwood M.; Kumar, Vipan

doi:10.1039/c3md00057e

Cited by 19 publications

(6 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…30–31 The synthesized conjugates proved to be potent against T. vaginalis exhibiting IC 50 values below 10 μM along with minimal cytotoxicity to cultured human cells. The methodology was further extended towards synthesis of N -propargylated-isatin Mannich adducts along with their in vitro evaluation against T. vaginalis and T. foetus with the most potent compound exhibiting an IC 50 value of 11.3 μM against T. foetus .…”

Section: Introductionmentioning

confidence: 99%

Design, synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins

et al. 2017

Self Cite

View full text Add to dashboard Cite

A series of N-alkyl tethered C-5 functionalized bis-isatins were synthesized and evaluated for antimicrobial activity against pathogenic microorganisms. The preliminary evaluation studies revealed the compound 4t, with an optimal combination of bromo-substituent at the C-5 position of isatin ring along with propyl chain linker being most active among the synthesized series exhibiting an IC50 value of 3.72 μM against Trichomonas vaginalis while 4j exhibited an IC50 value of 14.8 μM against Naegleria fowleri, more effective than the standard drug Miltefosine. The compound 3f with an octyl spacer length was the most potent among the series against Giardia lamblia with an IC50 of 18.4 μM while 3d exhibited an IC50 of 23 μM against Entamoeba histolytica. This library was also screened against the fungal pathogen Aspergillus parasiticus. A number of the compounds demonstrated potency against this fungus, illustrating a possible broad-spectrum activity. Furthermore, an evaluation of these synthesized compounds against a panel of normal flora bacteria revealed them to be non-cytotoxic, demonstrating the selectivity of these compounds. This observation, in combination with previous studies that isatin is non-toxic to humans, presents a new possible scaffold for drug discovery against these important protozoal pathogens of humans and animals.

show abstract

Section: Introductionmentioning

confidence: 99%

Design, synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

“…Remarkably, despite the good and high coverage of sanitary quality, these parasites are still a matter of concern to developed countries (e.g., in European countries and the North American states) ( Nisha et al., 2013 ; Gharpure et al., 2019 ). The outbreaks seem to be concentrated in the USA, Canada, Australia and the UK ( Karanis et al., 2007 ; Painter et al., 2016 ).…”

Section: Introductionmentioning

confidence: 99%

“…Each year, in the USA, 748,000 cases of cryptosporidiosis ( Scallan et al., 2011 ) and more than 1.2 million cases of G. intestinalis are diagnosed ( Collier et al., 2021 ). These parasites are zoonotic agents that are often identified during outbreaks caused by contaminated public water supplies ( Nisha et al., 2013 ; Painter et al., 2015 ). It is noteworthy that outbreaks of cryptosporidiosis have been related to public drinking water (failures at water treatment facilities), as in the massive Milwaukee cryptosporidiosis outbreak that affected nearly 400,000 people ( Mac Kenzie et al., 1994 ; Efstratiou et al., 2017 ).…”

Section: Introductionmentioning

confidence: 99%

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

Santos

Rebello

2022

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

Parasitic infections caused by protozoans that infect the mucosal surfaces are widely neglected worldwide. Collectively, Entamoeba histolytica, Giardia lamblia, Cryptosporidium spp. and Trichomonas vaginalis infect more than a billion people in the world, being a public health problem mainly in developing countries. However, the exact incidence and prevalence data depend on the population examined. These parasites ultimately cause pathologies that culminate in liver abscesses, malabsorption syndrome, vaginitis, and urethritis, respectively. Despite this, the antimicrobial agents currently used to treat these diseases are limited and often associated with adverse side effects and refractory cases due to the development of resistant parasites. The paucity of drug treatments, absence of vaccines and increasing problems of drug resistance are major concerns for their control and eradication. Herein, potential candidates are reviewed with the overall aim of determining the knowledge gaps and suggest future perspectives for research. This review focuses on this public health problem and focuses on the progress of drug repositioning as a potential strategy for the treatment of mucosal parasites.

show abstract

“…Eighteen of the synthesized hybrids have shown 100% growth inhibition at 100 mM with the most potent and non-cytotoxic compound showing and IC 50 of 7.69 mM. The methodology was further extended towards the synthesis of b-amino alcohol based blactameisatin conjugates and their evaluation against T. vaginalis at 50 mM with the most active chimeric scaffold among the test series exhibited an IC 50 of 9.73 mM along with low cytotoxicity [27]. As an extension of this work, we now describes the Cu(I)Cl-facilitated synthesis of N-propargylated-isatin Mannich adducts along with their preliminary in vitro evaluation studies against the veterinary protozoal pathogen T. foetus and cytotoxicity against human prostate (PC-3) cancer cell line.…”

Section: Introductionmentioning

confidence: 99%

N-Propargylated isatin-Mannich mono- and bis-adducts: Synthesis and preliminary analysis of in vitro activity against Tritrichomonas foetus

Nisha

Kumar

Bhargava

et al. 2014

European Journal of Medicinal Chemistry

Self Cite

View full text Add to dashboard Cite

Cu(I)Cl promoted synthesis of N-propargylated-isatin Mannich mono- and bis-adducts with an extension towards the synthesis of N-propargylated-isatin-7-chloroquinoline conjugates was described. The synthesized scaffolds were evaluated for their in vitro activity against the veterinary protozoal pathogen Tritrichomonas foetus and cytotoxicity against human prostate (PC-3) cancer cell line. The preliminary evaluation data revealed the enhancement in the activity profiles with the introduction of 7-chloroquinoline ring with the most active conjugates 7a, 7c and 7d exhibiting an IC₅₀ of 22.2, 11.3 and 24.5 μM respectively against T. foetus and minimal toxicity against human prostate (PC-3) cell lines.

show abstract

Design and synthesis of β-amino alcohol based β-lactam–isatin chimeras and preliminary analysis of in vitro activity against the protozoal pathogen Trichomonas vaginalis

Cited by 19 publications

References 33 publications

Design, synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins

Design, synthesis and preliminary antimicrobial evaluation of N-alkyl chain-tethered C-5 functionalized bis-isatins

An Overview of Mucosa-Associated Protozoa: Challenges in Chemotherapy and Future Perspectives

N-Propargylated isatin-Mannich mono- and bis-adducts: Synthesis and preliminary analysis of in vitro activity against Tritrichomonas foetus

Contact Info

Product

Resources

About