Abstract:Bacterial resistance to commonly used antibiotics has been recognized as a significant global health issue. In this study, we carried out the screening of a family of allylic thiocyanates for their action against a diversity of bacteria and fungi with a view to developing new antimicrobial agents. Allylic thiocyanates bearing halogenated aryl groups, which were readily obtained in two steps from the Morita-Baylis-Hillman adducts, showed moderate-to-high activity against selective pathogens, including a methici… Show more
“…Previous data showed that compound 11 exhibited moderate‐to‐good activity against C. albicans (12.5 μmol L −1 ) and C. tropicalis (25 μmol L −1 ); these findings corroborate to our results. Furthermore, compounds 8 , 9 , 11 and 14 inhibited MRSA growth, and thus demonstrated a broad spectrum of action against fungi and bacteria.…”
Section: Discussionsupporting
confidence: 93%
“…Previous data showed that compound 11 exhibited moderate‐to‐good activity against C. albicans (12.5 μmol L −1 ) and C. tropicalis (25 μmol L −1 ); these findings corroborate to our results. Furthermore, compounds 8 , 9 , 11 and 14 inhibited MRSA growth, and thus demonstrated a broad spectrum of action against fungi and bacteria. Compound 11 and bromo‐substituted analogues 8 and 9 exhibited promising antitubercular activity against replicating and non‐replicating forms of Mtb H 37 Rv (MIC 0.25 μmol L −1 ) with relatively low toxicity toward VERO cells .…”
Section: Discussionsupporting
confidence: 93%
“…Chain elongation was also deleterious to activity (see the cinnamoyl derivative ‐ compound 15 ; Supporting Information, Table S1) as well as the simultaneous presence of two substituents at the aromatic ring, such as in compounds 12 and 13 . Hence, our screening of the thiocyanates 1–15 against the present panel of fungi correlated with previous results for these compounds towards Mtb and bacteria, allowed us to select compound 11 as the best lead for further evaluation to develop a new broad spectrum drug and NE to treat microbial skin infections. Therefore, its mechanism of antifungal action, anti‐inflammatory capacity and toxicity were determined.…”
Section: Discussionsupporting
confidence: 77%
“…Allylic thiocyanates showed moderate‐to‐high activity against methicillin‐resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis (Mtb), human cancer cells and other targets . Therefore, we present the antifungal activity of functionalised allylic thiocyanates derived from the Morita‐Baylis‐Hillman reaction, as well as the toxicity and anti‐inflammatory properties of this collection of sulphur‐containing derivatives.…”
We report the antifungal and antichemotactic activities of a series of allylic thiocyanates with low toxicity. We also show improved antifungal activity of the most promising compound when used in a nanoemulsion (NE). The 4‐chlorophenyl‐substituted allylic thiocyanate (compound 11) exhibited a broad spectrum of antifungal activity and showed antichemotactic effects with 100% reduction in leucocyte migration. Minimal inhibitory concentrations ranged from 25 to 50 μg mL−1, and the mechanism of action was related to complexation with fungal ergosterol. The NE containing compound 11 enhanced the antifungal activity approximately 64‐fold for dermatophytes and 4‐fold for Candida spp.. Compound 11 was not mutagenic and did not cause cell death or significant haemoloysis, although it exhibited mild dose‐dependent DNA damage. It was not an irritant for chorioallantoic membrane of fertile white eggs and exhibited 100% inhibition of fungal growth in an in vivo model of dermatophytosis. Our data indicate that allylic thiocyanates are very promising for the antifungal potential in nanostructured systems, with associated anti‐inflammatory effect.
“…Previous data showed that compound 11 exhibited moderate‐to‐good activity against C. albicans (12.5 μmol L −1 ) and C. tropicalis (25 μmol L −1 ); these findings corroborate to our results. Furthermore, compounds 8 , 9 , 11 and 14 inhibited MRSA growth, and thus demonstrated a broad spectrum of action against fungi and bacteria.…”
Section: Discussionsupporting
confidence: 93%
“…Previous data showed that compound 11 exhibited moderate‐to‐good activity against C. albicans (12.5 μmol L −1 ) and C. tropicalis (25 μmol L −1 ); these findings corroborate to our results. Furthermore, compounds 8 , 9 , 11 and 14 inhibited MRSA growth, and thus demonstrated a broad spectrum of action against fungi and bacteria. Compound 11 and bromo‐substituted analogues 8 and 9 exhibited promising antitubercular activity against replicating and non‐replicating forms of Mtb H 37 Rv (MIC 0.25 μmol L −1 ) with relatively low toxicity toward VERO cells .…”
Section: Discussionsupporting
confidence: 93%
“…Chain elongation was also deleterious to activity (see the cinnamoyl derivative ‐ compound 15 ; Supporting Information, Table S1) as well as the simultaneous presence of two substituents at the aromatic ring, such as in compounds 12 and 13 . Hence, our screening of the thiocyanates 1–15 against the present panel of fungi correlated with previous results for these compounds towards Mtb and bacteria, allowed us to select compound 11 as the best lead for further evaluation to develop a new broad spectrum drug and NE to treat microbial skin infections. Therefore, its mechanism of antifungal action, anti‐inflammatory capacity and toxicity were determined.…”
Section: Discussionsupporting
confidence: 77%
“…Allylic thiocyanates showed moderate‐to‐high activity against methicillin‐resistant Staphylococcus aureus (MRSA), Mycobacterium tuberculosis (Mtb), human cancer cells and other targets . Therefore, we present the antifungal activity of functionalised allylic thiocyanates derived from the Morita‐Baylis‐Hillman reaction, as well as the toxicity and anti‐inflammatory properties of this collection of sulphur‐containing derivatives.…”
We report the antifungal and antichemotactic activities of a series of allylic thiocyanates with low toxicity. We also show improved antifungal activity of the most promising compound when used in a nanoemulsion (NE). The 4‐chlorophenyl‐substituted allylic thiocyanate (compound 11) exhibited a broad spectrum of antifungal activity and showed antichemotactic effects with 100% reduction in leucocyte migration. Minimal inhibitory concentrations ranged from 25 to 50 μg mL−1, and the mechanism of action was related to complexation with fungal ergosterol. The NE containing compound 11 enhanced the antifungal activity approximately 64‐fold for dermatophytes and 4‐fold for Candida spp.. Compound 11 was not mutagenic and did not cause cell death or significant haemoloysis, although it exhibited mild dose‐dependent DNA damage. It was not an irritant for chorioallantoic membrane of fertile white eggs and exhibited 100% inhibition of fungal growth in an in vivo model of dermatophytosis. Our data indicate that allylic thiocyanates are very promising for the antifungal potential in nanostructured systems, with associated anti‐inflammatory effect.
“…It was shown that a piperidine isoselenocyanate derivative is the most active among its isosters against selected fungi, including Fusarium culmorum . Furthermore, related thiocyanates exhibit a variety of biological properties,, including antibacterial activity against Mycobacterium tuberculosis and methicillin‐resistant Staphylococcus aureus (MRSA) . These facts motivate the investigation of allylic organoselenium compounds as antifungal agents.…”
Fusarium is an emerging opportunistic fungal pathogen that causes local or systemic infections. The successful use of a therapeutic drug or combination antifungal therapies against Fusarium spp. are compromised because reports of multidrug resistance are currently frequent. Thus, the development of new antifungal capable of combating multidrug‐resistant Fusarium strains becomes necessary. This study presents the synthesis of seven new allylic selenocyanates and their screening against Fusarium spp. Minimum inhibitory concentrations (MICs) of these compounds ranged from 4 to 64 μg mL−1, with the mechanism of action being related to fungal cell membrane disruption. Specific structural changes, such as widespread thinning along the hyphae, were observed by scanning electron microscopy. The effect of selenocyanates on cell viability and genotoxicity are concentration dependent, however they did not cause mutagenicity in human cells. Five selenocyanates were identified as nonirritant by the ex‐vivo HET‐CAM (Hen′s Egg Test‐Chorioallantoic Membrane) method. Allylic selenocyanates represents a promising alternative in the treatment and prevention of fusariosis.
Methods for the synthesis of a variety of functionalized 2‐iminothiazolidines and related heterocycles through a base‐mediated domino nucleophilic displacement/intramolecular anti‐Michael addition process involving electron‐deficient allylic bromides and 1,3‐ambident nucleophiles derived from thiourea were developed. These transformations proceed under mild and simple conditions and different functional groups are well tolerated. The scope and limitations of this protocol are dependent on the structure of the allylic bromide and 1,3‐ambident nucleophile involved. The synthetic versatility of 2‐iminothiazolidines was further demonstrated through a series of chemoselective modifications, giving rise to a wide range of thiazolidine frameworks of structural complexity. In particular, the reductive cyclization of 2‐nitrobenzyl‐substituted 2‐iminothiazolidines furnished novel spiroquinolones in good to fair yields. The structural assignment of key products was unequivocally achieved by X‐ray diffraction analysis and two‐dimensional NMR techniques.
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