Synthesis and bioactivities of Phenazine-1-carboxylic acid derivatives based on the modification of PCA carboxyl group

• Published in: Bioorganic & medicinal chemistry letters Vol. 27; no. 9; pp. 2010 - 2013
• Main Authors: Xiong, Zhipeng, Niu, Junfan, Liu, Hao, Xu, Zhihong, Li, Junkai, Wu, Qinglai
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.05.2017; Elsevier
• Subjects: Carboxyl group; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Derivatives; Fungicidal activity; Fungicides, Industrial - chemical synthesis; Fungicides, Industrial - chemistry; Fungicides, Industrial - toxicity; Fusarium - drug effects; Life Sciences & Biomedicine; Oryza - microbiology; Pharmacology & Pharmacy; Phenazine-1-carboxylic acid; Phenazines - chemical synthesis; Phenazines - chemistry; Phenazines - toxicity; Physical Sciences; Plant Diseases - microbiology; Plant Diseases - prevention & control; Rhizoctonia - drug effects; Science & Technology; Structure-Activity Relationship; Synthesis; Triticum - microbiology; Carboxyl group; Phenazine-1-carboxylic acid; Synthesis; Derivatives; Fungicidal activity; METABOLITES; RHIZOCTONIA; PSEUDOMONAS; RESISTANCE; RICE SHEATH BLIGHT; OPTIMIZATION; Phenazine-l-carboxylic acid; INHIBITORS; MAIZE; FUSARIUM-GRAMINEARUM
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2017.03.011

The synthesis and bioactivities of Phenazine-1-carboxylic acid derivatives based on the modification of PCA carboxyl group were studied systematically. To find higher fungicidal activities compounds and study the effects on fungicidal activities after changing the carboxyl group of PCA, we synthesized a series of Phenazine-1-carboxylic acid derivatives by modifying the carboxyl group of PCA as much as possible. The results of structure–activity analysis indicated that the carboxyl group of PCA could be modified to be amide group, acylhydrazine group, ester group, methyl, hydroxymethyl, chloromethyl and ether group etc. And appropriate modification on carboxyl group of PCA was useful to extending the fungicidal scope. [Display omitted] Phenazine-1-carboxylic acid (PCA) as a natural product widely exists in microbial metabolites of Pseudomonads and Streptomycetes and has been registered for the fungicide against rice sheath blight in China. To find higher fungicidal activities compounds and study the effects on fungicidal activities after changing the carboxyl group of PCA, we synthesized a series of PCA derivatives by modifying the carboxyl group of PCA and their structures were confirmed by 1H NMR and HRMS. Most compounds exhibited significant fungicidal activities in vitro. In particular, compound 6 exhibited inhibition effect against Rhizoctonia solani with EC50 values of 4.35mg/L and compound 3b exhibited effect against Fusarium graminearum with EC50 values of 8.30mg/L, compared to the positive control PCA with its EC50 values of 7.88mg/L (Rhizoctonia solani) and 127.28mg/L (Fusarium graminearum), respectively. The results indicated that the carboxyl group of PCA could be modified to be amide group, acylhydrazine group, ester group, methyl, hydroxymethyl, chloromethyl and ether group etc. And appropriate modifications on carboxyl group of PCA were useful to extend the fungicidal scope.