Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

Lavorato, Stefânia Neiva; Duarte, Mariana C.; Andrade, Pedro H.R.; Coelho, Eduardo Antônio Ferraz; Alves, Ricardo José

doi:10.1590/s2175-97902017000116067

Cited by 9 publications

(17 citation statements)

References 29 publications

(27 reference statements)

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“…These results corroborate the finding by Lavorato et al and Serafim et al with some compounds of the same class investigated in this study: for meta ‐substituted compounds, it was observed that the electronic effect of ring substituent has a greater influence on biological activity of this chemical class . One hundred and twenty‐one compounds were analysed in our study to follow the sequence of molecules also tested by our group for antiprotozoal and antibacterial . This relevant number of synthetic compounds comprised structures of five different chemical classes with varying substituents.…”

Section: Resultssupporting

confidence: 91%

“…Usually, a SI value higher than 10 is recommended to ensure the safety of an antimicrobial substance . The higher the SI value of a substance, the better its selective performance against the pathogen and the lower the toxicity against the studied host cell (lymphocytes) . In this study, the only compound with IS > 10 was the 2j , which presented the safest biological profile with selectivity against dermatomycosis fungi.…”

Section: Resultsmentioning

confidence: 76%

“…The SI for the active compounds presented in Table corresponds to the ratio between the IC 50 (concentration required to inhibit 50% of the human lymphocytes viability) and the average of subinhibitory concentrations (MIC/2; MICs are presented in Table ) for dermatophytes and Candida spp. Usually, a SI value higher than 10 is recommended to ensure the safety of an antimicrobial substance . The higher the SI value of a substance, the better its selective performance against the pathogen and the lower the toxicity against the studied host cell (lymphocytes) .…”

Section: Resultsmentioning

confidence: 99%

“…In total, 121 compounds were evaluated for antifungal activity: group (1)—1,3‐bis(aryloxy)‐2‐propanol derivatives ( 1a – 1gg ; 33 compounds), group (2)—1,3‐bis(aryloxy)‐2‐propanamine derivatives ( 2a – 2bb ; 28 compounds), group (3)—2‐(2‐oxo‐2(arylamino)ethyl)isothiouronium chloride derivatives ( 3a – 3j ; 10 compounds), group (4)—1,3‐bis(aryloxy)‐2‐methanesulfonyloxypropane derivatives ( 4a – 4y ; 25 compounds) and group (5)—1,3‐bis(aryloxy)‐2‐azidopropane derivatives ( 5a – 5y ; 25 compounds). The compounds were synthesised according to Lavorato et al All reagents were obtained from commercial suppliers and used without further purification. Melting points were determined on Microquímica MQAPF 301 apparatus.…”

Section: Methodsmentioning

confidence: 99%

“…In total, 121 compounds were evaluated for antifungal activity: 23,24 All reagents were obtained from commercial suppliers and used without further purification. Pfizer.…”

Section: Chemicals-general Procedures For Synthesis Of Compoundsmentioning

confidence: 99%

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Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

Lana

Lavorato

Giuliani

et al. 2019

Mycoses

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Summary Background Fungal infections are highly prevalent and are responsible for high rates of morbidity and mortality. In this context, the search for new treatment alternatives is very relevant. Objectives Analyse chemical compounds for antifungal potential against dermatomycosis fungi. Methods The antifungal activity of 121 compounds, intermediates or derivatives of 1,3‐bis(aryloxy)propane substituted at C‐2 (111 compounds) and isothiouronium derivatives (10 compounds) was investigated through susceptibility tests, mechanism of action, toxicity and hydrogel incorporation. Results The compound 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride (2j) was the most active fungicide against dermatophytes and Candida spp., at very low concentrations (0.39‐3.12 µg/mL), including action on resistant and multidrug‐resistant clinical strains. Compound 2j has presented a promising toxicity profile, showing selectivity index >10, relative to human lymphocytes. The compound was classified as non‐irritant by the HET‐CAM test and did not cause histopathological alterations in pig ear skin, thus presenting an excellent perspective for topical application. 2j targets the fungal cell wall, which was confirmed by scanning electron microscopy, which also indicated the additional ability of 2j to inhibit the Candida albicans pseudohyphae formation and biofilm of Microsporum canis. Compound 2j was incorporated in a hydrogel with bioadhesive potential. The results of the human skin permeation showed that 2j remained significantly in the epidermis, ideally for the dermatomycosis treatment. Conclusions Therefore, the compound 2j demonstrated the potential for antifungal drug development, with a action mechanism elucidated and already applied in a semisolid formulation as a new therapeutic option for fungal skin infections.

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Section: Resultssupporting

confidence: 91%

Section: Resultsmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…In total, 121 compounds were evaluated for antifungal activity: 23,24 All reagents were obtained from commercial suppliers and used without further purification. Pfizer.…”

Section: Chemicals-general Procedures For Synthesis Of Compoundsmentioning

confidence: 99%

See 3 more Smart Citations

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

Lana

Lavorato

Giuliani

et al. 2019

Mycoses

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A Film‐Forming System Hybridized with a Nanostructured Chloroacetamide Derivative for Dermatophytosis Treatment

et al. 2021

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Dermatophytosis is the fourth cause of infectious disease in the world, affecting about 40 % of the population. Thus, the prospection for new agents and the new formulations with antifungal potential is necessary. This study evaluated the antidermatophytic activity of a nanostructure (NS) containing a chloroacetamide derivative (4-BFCA-NS) as well as its doseresponse kinetics and skin adhesive property when associated to a film-forming system (4-BFCA-NS-FFS), forming a hybrid. The dose-response curves of 4-BFCA-NS and 4-BFCA-NS-FFS were evaluated by time-kill assay. A texture analyzer was used for evaluated the skin adhesive property of the formulations. NS presented a nanometric size, monomodal distribution, positive zeta potential, and slightly acidic pH. 4-BFCA-NS maintained the anti-dermatophytic action of 4-BFCA (MIC range 6.25-25 μg ml À 1 ). 4-BFCA-NS-FFS hybrid presented a fungicidal action and skin adhesive capacity, suggesting its applicability as a new topical formulation for the treatment of superficial and cutaneous dermatophytosis.

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Pharmacological and physicochemical profile of arylacetamides as tools against human cancers

Ferreira

Machado

Lavorato

et al. 2019

Toxicology and Applied Pharmacology

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Synthesis, antileishmanial activity and QSAR studies of 2-chloro- N -arylacetamides

Cited by 9 publications

References 29 publications

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

Discovery of a novel and selective fungicide that targets fungal cell wall to treat dermatomycoses: 1,3‐bis(3,4‐dichlorophenoxy)propan‐2‐aminium chloride

A Film‐Forming System Hybridized with a Nanostructured Chloroacetamide Derivative for Dermatophytosis Treatment

Pharmacological and physicochemical profile of arylacetamides as tools against human cancers

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