Design, Synthesis, Antibacterial, and Antifungal Evaluation of Phenylthiazole Derivatives Containing a 1,3,4-Thiadiazole Thione Moiety.

To effectively control the infection of plant pathogens, we designed and synthesized a series of phenylthiazole derivatives containing a 1,3,4-thiadiazole thione moiety and screened for their antibacterial potencies against Ralstonia solanacearum, Xanthomonas oryzae pv. oryzae, as well as their antifungal potencies against Sclerotinia sclerotiorum, Rhizoctonia solani, Magnaporthe oryzae and Colletotrichum gloeosporioides. The chemical structures of the target compounds were characterized by 1H NMR, 13C NMR and HRMS. The bioassay results revealed that all the tested compounds exhibited moderate-to-excellent antibacterial and antifungal activities against six plant pathogens. Especially, compound 5k possessed the most remarkable antibacterial activity against R. solanacearum (EC50 = 2.23 µg/mL), which was significantly superior to that of compound E1 (EC50 = 69.87 µg/mL) and the commercial agent Thiodiazole copper (EC50 = 52.01 µg/mL). Meanwhile, compound 5b displayed the most excellent antifungal activity against S. sclerotiorum (EC50 = 0.51 µg/mL), which was equivalent to that of the commercial fungicide Carbendazim (EC50 = 0.57 µg/mL). The preliminary structure-activity relationship (SAR) results suggested that introducing an electron-withdrawing group at the meta-position and ortho-position of the benzene ring could endow the final structure with remarkable antibacterial and antifungal activity, respectively. The current results indicated that these compounds were capable of serving as promising lead compounds.

Synthesis of Imidazo[1,2-a]pyridine-Fused 1,3-Benzodiazepine Derivatives with Anticancer Activity via a One-Pot Cascade GBB-3CR/Pd(II)-Catalyzed Azide-Isocyanide Coupling/Cyclization Process.

A new one-pot synthesis of imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives via a sequential GBB-3CR/Pd(II)-catalyzed azide-isocyanide coupling/cyclization process was developed. The Groebke-Blackburn-Bienaymé three-component reactions (GBB-3CR) of 2-aminopyridine, 2-azidobenzaldehydes, and isocyanides in the presence of a catalytic amount of p-toluenesulfonic acid gave azide intermediates without separation. The reaction was followed by using another molecule of isocyanides to produce imidazo[1,2-a]pyridine-fused 1,3-benzodiazepine derivatives in good yields by the Pd(II)-catalyzed azide-isocyanide coupling/cyclization reaction. The synthetic approach produces novel nitrogen-fused polycyclic heterocycles under mild reaction conditions. The preliminary biological evaluation demonstrated that compound 6a inhibited glioma cells efficiently, suggesting potentially broad applications of the approach for synthesis and medicinal chemistry.

Design, synthesis and antifungal evaluation of phenylthiazole-1,3,4-oxadiazole thione (ketone) derivatives inspired by natural thiasporine A.

BACKGROUND: Plant pathogenic fungal infections have become a severe threat to the yield and quality of agricultural products, and new green antifungal agents with high efficiency and low toxicity are needed. In this study, a series of thiasporine A derivatives containing phenylthiazole-1,3,4-oxadiazole thione (ketone) structures were designed and synthesized, and their antifungal activities against six invasive and highly destructive phytopathogenic fungi were evaluated. RESULTS: The results found that all compounds showed moderate to potent antifungal activity against six phytopathogenic fungi, and most of the E series compounds showed remarkable antifungal activity against Sclerotinia sclerotiorum and Colletotrichum camelliaet. In particular, compounds E1-E5, E7, E8, E13, E14, E17, and E22 showed more significant antifungal activity against S. sclerotiorum, with half-maximal effective concentration (EC50 ) values of 0.22, 0.48, 0.56, 0.65, 0.51, 0.39, 0.60, 0.56, 0.60, 0.63, and 0.45 µg mL-1 , respectively, which were superior to that of carbendazim (0.70 µg mL-1 ). Further activity studies showed that compound E1 possessed superior curative activities against S. sclerotiorum in vivo and better inhibitory effects on sclerotia germination and the formation of S. sclerotiorum compared with those of carbendazim. CONCLUSIONS: This study indicates that these thiasporine A derivatives containing phenylthiazole-1,3,4-oxadiazole thione structures might be used as antifungal agents against S. sclerotiorum. © 2023 Society of Chemical Industry.