Discovery and Mechanism of Azatryptanthrin Derivatives as Novel Anti-Phytopathogenic Bacterial Agents for Potent Bactericide Candidates

Abstract

The natural alkaloids of tryptanthrin and their derivatives have a wide range of biological activities. In this research, four series of azatryptanthrin derivatives containing 4-aza/3-aza/2-aza/1-aza tryptanthrin were prepared by condensation cyclization reaction against plant pathogens to develop a new natural product-based bacterial pesticide. Compound 4Aza-8 displayed a remarkable growth inhibitory effect on pathogenic bacteria of Xanthomonas axonopodis pv. citri (Xac), Xanthomonas oryzae pv. Oryzae (Xoo), and Pseudomonas syringae pv. actinidiae (Psa) with the final corrected EC 50 values of 0.312, 1.91, and 18.0 μg/mL, respectively, which were greatly superior than that of tryptanthrin (Tryp). Moreover, 4Aza-8 also showed effective therapeutic and protective activities in vivo on citrus canker. Further mechanism studies on Xac elucidated that compound 4Aza-8 was able to affect the growth curve of Xac and the formation of biofilm, cause severe shrinkage in bacterial morphology, increase reactive oxygen species levels, and induce apoptosis in bacterial cells. Quantitative analysis of differential protein profiles found that the major differences were mainly concentrated on the endometrial protein in the bacterial secretion system pathway, which blocked the membrane transport and affected the transfer of DNA to the host cell. In summary, these research results suggest that 4Aza-8 represents a promising anti-phytopathogenic-bacteria agent, which is worth being further investigated as a bactericide candidate.

Novel 5-Sulfonyl-1,3,4-thiadiazole-Substituted Flavonoids as Potential Bactericides and Fungicides: Design, Synthesis, Three-Dimensional Quantitative Structure–Activity Relationship Studies

“…The in vitro antibacterial activity of the target compounds against two pathogenic bacteria ( Xoo and Xac ) was assessed by using the classic turbidimetric method. Furthermore, based on previous reports, the activity of compounds 1 – 34 against rice leaf blight in a living pot was studied, and the listed drug bismerthiazole (Bis) was used as a control. , …”

Design, Synthesis, and Mechanism of Novel 9-Aliphatic Amine Tryptanthrin Derivatives against Phytopathogenic Bacteria

“…In vitro bioassays were conducted against three pathogenic bacteria ( Xac , Xoo , and Psa ), followed by in vivo bioassays against citrus bacterial canker as per our previous research. – …”

Recent advances of tryptanthrin and its derivatives as potential anticancer agents

“…The substitution of halogen, alkyl and alkoxy groups onto the A and D aromatic rings has been investigated by Liu, Sharma and other groups. [49][50][51][52][53][54][55][56][57][58][59][60][61][62] A series of substituted tryptanthrins (11)(12)(13)(14)(15)(16)(17)(18)(19) are prepared by the optimized Bergman condensation reaction of substituted isatins with substituted isatoic anhydrides (Scheme 3). The usage of substituted anilines as reaction materials to prepare substituted isatin derivatives needs two steps.…”

“…11 Subsequently, the study on tryptanthrin alkaloid was discussed in another review article in 2013, where various synthetic methods were applied for the preparation of tryptanthrin. 12a Owing to its pharmacologically aromatic indoloquinazoline moiety with a wide range of biological and pharmacological activities, tryptanthrin has been extensively applied as a parental backbone via the modification of different functional groups for the development of new tryptanthrin derivatives with significant medicinal benefits as antitrypanosomal, 13 antifungal, 14,15 anti-phytopathogenic bacterial, 16 antibacterial, [17][18][19][20][21] anti-MRSA, 22 antiviral, [23][24][25][26] antiangiogenic, 27 anti-inflammatory, [28][29][30][31][32][33][34][35][36][37][38][39] anti-leishmanial, 40,41 antimalarial, 42 antiplasmodial, 43 antiparasitic, 44 antitubercular, [45][46][47] and anti-cancer [48][49][50][51][52][53][54]…”