Synthesis and antileishmanial activity of 1,3-bis(aryloxy)propan-2-amines

Lavorato, Stefânia Neiva; Duarte, Mariana C.; Lage, Daniela P.; Tavares, Carlos Alberto Pereira; Coelho, Eduardo Antônio Ferraz; Alves, Ricardo José

doi:10.1007/s00044-017-1805-1

Cited by 11 publications

(23 citation statements)

References 29 publications

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“…The cytotoxic concentration of 50% (CC 50 ) of active compounds in mammalian cells was generally also in the low micromolar range, corroborating the results obtained by Lavorato et al. (). Hence, the selectivity index (SI) values obtained ranged from 0.25 to 2.19.…”

Section: Discussionsupporting

confidence: 89%

“…These compounds, named as CPD1–CPD22, were synthesized in four steps (Figure ), as previously described by Lavorato et al. ().…”

Section: Resultsmentioning

confidence: 99%

“…CPD37 was obtained as previously described by Lavorato et al. (). The ketone CPD38 was obtained from CPD37 by Albright–Goldman oxidation using DMSO and acetic anhydride (Fritsche, Elfringhoff, Fabian, & Lehr, ), while the tosylate CPD39 was prepared by reacting CPD37 with p ‐toluenesulfonyl chloride in dry pyridine (King & Bigelow, ).…”

Section: Resultsmentioning

confidence: 99%

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Antibacterial activity of synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive bacteria

et al. 2019

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Synthetic 1,3‐bis(aryloxy)propan‐2‐amines have been shown in previous studies to possess several biological activities, such as antifungal and antiprotozoal. In the present study, we describe the antibacterial activity of new synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive pathogens (Streptococcus pyogenes, Enterococcus faecalis and Staphylococcus aureus) including Methicillin–resistant S. aureus strains. Our compounds showed minimal inhibitory concentrations (MIC) in the range of 2.5–10 μg/ml (5.99–28.58 μM), against different bacterial strains. The minimal bactericidal concentrations found were similar to MIC, suggesting a bactericidal mechanism of action of these compounds. Furthermore, possible molecular targets were suggested by chemical similarity search followed by docking approaches. Our compounds are similar to known ligands targeting the cell division protein FtsZ, Quinolone resistance protein norA and the Enoyl‐[acyl‐carrier‐protein] reductase FabI. Taken together, our data show that synthetic 1,3‐bis(aryloxy)propan‐2‐amines are active against Gram‐positive bacteria, including multidrug–resistant strains and can be a promising lead in the development of new antibacterial compounds for the treatment of these infections.

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Section: Discussionsupporting

confidence: 89%

“…These compounds, named as CPD1–CPD22, were synthesized in four steps (Figure ), as previously described by Lavorato et al. ().…”

Section: Resultsmentioning

confidence: 99%

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Antibacterial activity of synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive bacteria

et al. 2019

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“…Structurally, the position of the chlorine is important for improving the antifungal action, since the substitution at positions meta and para of the disubstituted molecule 2j was more advantageous (lower MICs) than the substitution at ortho and para positions as for 2i (Figure ). 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 .…”

Section: Resultssupporting

confidence: 92%

“…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%

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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Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure–activity relationship

et al. 2020

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Synthesis and antileishmanial activity of 1,3-bis(aryloxy)propan-2-amines

Cited by 11 publications

References 29 publications

Antibacterial activity of synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive bacteria

Antibacterial activity of synthetic 1,3‐bis(aryloxy)propan‐2‐amines against Gram‐positive bacteria

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

Imidazole derivatives as antiparasitic agents and use of molecular modeling to investigate the structure–activity relationship

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