Synthesis, Antibacterial Activity, and Mechanisms of Novel Indole Derivatives Containing Pyridinium Moieties

Abstract

The development of effective antibacterial agents equipped with novel action modes and unique skeletons starting from natural compounds serves as an important strategy in the modern pesticide industry. Disclosed here are a series of novel indole derivatives containing pyridinium moieties and their antibacterial activity evaluation against two prevalent phytopathogenic bacteria, Xanthomonas oryzae pv. oryzicola (Xoc) and X. oryzae pv. oryzae (Xoo). A three-dimensional (3D)-QSAR model was adopted to discover higher activity like title compounds based on the Xoc antibacterial activity of the tested compounds. Compound 43 was consequently designed, and it displayed higher antibacterial activity as expected with the half-maximal effective concentration EC50 values of 1.0 and 1.9 μg/mL for Xoo and Xoc, respectively, which were better than those of the commercial drug thiodiazole copper (TC) (72.9 and 87.5 μg/mL). Under greenhouse conditions, the results of a rice in vivo pot experiment indicated that the protective and curative activities of compound 43 against rice bacterial leaf streak (BLS) and rice bacterial blight (BLB) were 45.0 and 44.0% and 42.0 and 39.3%, respectively, which were better than those of the commercial agent thiodiazole copper (38.0 and 37.9%, 38.6 and 37.0%) as well. Scanning electron microscopy images, defense enzyme activity tests, and proteomic techniques were utilized in a preliminary mechanism study, suggesting that compound 43 shall modulate and interfere with the physiological processes and functions of pathogenic bacteria.

The role of indole derivative in the growth of plants: A review

“…In 2022, Li et al reported that indole derivatives 29 (Figure 5) containing pyridinium salts could regulate the conversion of glycolysis in rice to produce pyruvate, which was further decarboxylated to produce acetyl-CoA and subsequently entered the citric acid cycle where NAD + was reduced to NADH. The NADH produced by this process was fed into the oxidative phosphorylation way (Li et al, 2022a). The result of the two closely linked ways improves plant resistance to Xanthomonas oryzae pv.…”

Synthesis and Biological Evaluation of Piperazine Hybridized Coumarin Indolylcyanoenones with Antibacterial Potential

“…Cyanoenone is an extended fragment of enone, in which cyano and carbonyl groups have the potential to interact with DNA or enzymes through hydrogen bonds, exists in various drugs, such as entacapone, teriflunomide ( Figure 1 ), and bardoxolone, exhibiting a broad range of pharmacological activities. Indole is a fused nitrogen-containing heterocycle, which can be used as a signal molecule to modulate multiple biological processes, including bacterial pathogenesis [ 23 , 24 , 25 ], and has been presented in many important pharmaceuticals, such as indolmycin, daptomycin, and indomethacin, displaying good pharmacokinetic properties [ 26 , 27 , 28 ]. Hence, introducing indolylcyanoenone composed of indole and cyanoenone into the coumarin scaffold might be an effective strategy to construct a new antibacterial framework against drug-resistant bacteria.…”

Splicing Indoles and 4,5-Dihydro-1H-pyrazoline Structure Gave Birth to Novel Antiviral Agents: Design, Synthesis, and Mechanism Study

“…Indole and its derivatives have received copious attention for their physicochemical and pharmacological properties. Meanwhile, indole derivatives have broad-spectrum biological activities, such as antibacterial, − anti-inflammatory, − and antiviral. − Therefore, commercial products with an indole backbone can be continually searched for in research and development in pesticides and pharmaceuticals. Recent studies have shown that the antiviral mechanism of most indole-containing compounds increases the plant body’s autoimmunity to fulfill disease rebellion. − As a promising moiety in this category, 4,5-dihydro-1 H -pyrazoline exhibits diverse activities, which have led to the development of numerous commercially available drugs for application to insecticides, − antivirals, − herbicides, − and fungicides. − Thiourea is likewise an active structure, and its most well-known feature is its ability to serve as a hydrogen bond former, which helps strengthen the molecule’s binding to the probable target.…”