Design, synthesis, and antifungal activity of novel cinnamon–pyrazole carboxamide derivatives

Abstract

Hit, Lead & Candidate Discovery To discover succinate dehydrogenase inhibitors with a novel structure, we introduced cinnamic acid structure to optimize the lead structure 1 and synthesized four series of cinnamon–pyrazole carboxamide derivatives. The bioassay data showed that compounds (E)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl)‐3‐(2‐fluorophenyl) acrylamide (5III‐d) and (E)‐3‐(2‐chlorophenyl)‐N‐(1‐[4‐chlorophenyl]‐4‐cyano‐1H‐pyrazol‐5‐yl) acrylamide (5III‐f) showed the significant antifungal activity against three fungi. In addition, 5III‐d and 5III‐f exhibited the excellent inhibitory effect against succinate dehydrogenase (SDH) enzymes with IC50 values ranging from 19.4 to 28.7 μM. The study demonstrates that the chlorine substituent group is present on both the phenyl and pyrazole rings that have a very good effect on the antifungal effect, and the compounds 5III‐d and 5III‐f can act as potential SDH inhibitors (SDHI) and throw a sprat for a new generation of SDHI.

Studies on the novel pyridine sulfide containing SDH based heterocyclic amide fungicide

“…1). 15,16 At present, five commercial SDHI fungicides have been successfully developed by structural modification of the amide bridge, including isofetamid, 17 fluopyram, 18 pydiflumetofen, 19 isoflucypram 20 and pyrapropoyne. 21 Fluopyram (Fig.…”

Novel 5‐(1‐aryl‐1H‐pyrazol‐3‐yl)‐1H‐tetrazoles as glycogen phosphorylase inhibitors: An in vivo antihyperglycemic activity study

“…Particularly, five‐ and six‐membered heterocyclic systems are motifs of many efficacious drugs (Figure ). Pyrazoles are well‐known examples of aromatic five‐membered heterocyclic organic compounds containing two adjacent nitrogen atoms endowed with diverse biological activity on humans such as antimicrobial (Sridhar et al, ), antidiabetic, anticancer (Altıntop, Ozdemir, Ilgın, & Atli, ), anti‐inflammatory (Raffa et al, ; Ren et al, ), antiviral (El‐Sabbagh et al, ), anticonvulsant, and antidepressant (Abdel‐Aziz, El‐Din, Abuo‐Rahma, & Hassan, ). Furthermore, the pyrazole derivatives are used as synthon for the development of condensed heterocyclic scaffolds and thus signify as interesting template for combinational chemistry (Singh, Paul, & Holzer, ; Tiwari, Ameta, Ranwal, Ameta, & Punjabi, ).…”

Rapid elimination of foodborne and environmental fungal contaminants by benzo analogs

“…The study showed that methylcellulose also played a role in CA retention in the tongue tissue of the Candida ‐infected mouse, while CA was not detected in blood, thus indicating materials, such as methylcellulose, could also be used as a tool for the treatment of local (oral) candidiasis . The cinnamic acid moiety has been used / introduced further into the lead structure of other candidate compounds to develop succinate dehydrogenase inhibitor for fungal treatment …”

“…25 The cinnamic acid moiety has been used / introduced further into the lead structure of other candidate compounds to develop succinate dehydrogenase inhibitor for fungal treatment. 26 Collectively, studies indicated the important role of hydrocarbon side chain of CA for high-potency antifungal activity. Elucidation of precise structure-activity relationship of test compounds for their antifungal efficacy in different food matrices warrants future investigation.…”