Synthesis and Antibacterial Activity of Novel 1H‐indol‐2‐ol Derivatives

A series of novel 1H‐indol‐2‐ol derivatives were synthesized and evaluated their antibacterial activities against rice bacterial leaf blight, tobacco bacterial wilt, and citrus canker caused by Xanthomonas oryzae pv. oryzae (Xoo), Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri via the turbidimeter test in vitro. Antibacterial bioassay indicated that most compounds demonstrated good inhibitory effect against Xoo and Ralstonia solanacearum. Especially, compound 4k demonstrated the best inhibitory effect against Xoo with half‐maximal effective concentration (EC₅₀) value of 8.27 μg/mL, which was even better than those of commercial agents Bismerthiazol and Thiodiazole copper.     

Synthesis and biological evaluation of 1,4-pentadien-3-one derivatives containing 1,2,4-triazole

A series of new 1,4-pentadien-3-one derivatives containing 1,2,4-triazole moiety were synthesized. The structures of the synthesized compounds were charactered via ¹H NMR, ¹³C NMR and HRMS. Antibacterial bioassays indicated that some of compounds showed potential antibacterial activities against Ralstonia solanacearum (Rs), Xanthomonas oryzae pv. Oryzae (Xoo) and Xanthomonas axonopodis pv. Citri (Xac). Compounds F₈ and F₁₇ showed good in vitro antibacterial activities against Rs, with the EC₅₀ values of 18.6 and 18.6 μg/mL, respectively, which were better than commercial agent bismerthiazol (55.2 μg/mL). Furthermore, compounds F₁₂ and F₁₅ showed good in vitro antibacterial activities against Xoo, with the EC₅₀ values of 10.9 and 17.5 μg/mL, which were better than commercial agent bismerthiazol (69.3 μg/mL). Moreover, compounds F₂, F₉, F₁₆ and F₁₇ showed good in vitro antibacterial activities against Xac, with the EC₅₀ values of 6.6, 5.4, 7.5 and 7.8 μg/mL, respectively, which were better than commercial agent bismerthiazol (54.9 μg/mL). The effect of compound F₉ on Xac bacterial cell membrane rupture was observed by scanning electron microscopy (SEM). In addition, antiviral bioassays indicated that some of compounds showed excellent protection activities against tobacco mosaic virus (TMV). Compounds F₅ and F₁₅ showed good protecting activity against TMV, with the EC₅₀ values of 108.3 and 105.4 μg/mL, respectively, which were better than commercial agent ningnanmycin (214.7 μg/mL). Microscale thermophoresis (MST) also showed that the binding of compound F₂ to TMV coat protein (TMV-CP) yielded a Kd value of 1.260 ± 0.654 μmol/L, which was very close to ningnanmycin (1.058 ± 0.286 μmol/L). Similarly, the molecular docking studies for F₂ and F₅ with TMV-CP (PDB code: 1EI7, ID: 4QGH) indicated that compounds F₂ and F₅ had partially interacted with TMV-CP.     

Synthesis and Evaluation of 1,3,4‐Thiadiazole Derivatives Containing Cyclopentylpropionamide as Potential Antibacterial Agent

This study aimed to identify new strategies for the control of these plant bacterial diseases by combining a pharmacophoric group of different bioactive compounds. A series of 3‐cyclopentylpropionamide containing 1,3,4‐thiadiazole derivatives was synthesized and characterized via ¹H‐NMR, ¹³C‐NMR, and HRMS. Bioassay results indicated that compounds 7a , 7d , 7j , 7m , 7n , and 7s had excellent antibacterial activity compared with the positive control. Among them, compound 7a exhibited remarkable inhibitory effect against Xoo with an EC₅₀ of 21.41 μg/mL, which surpassed that of thiodiazole copper (67.71 μg/mL) and bismerthiazol (69.05 μg/mL). Greenhouse condition tests further revealed that 7a had approximately equal curative activity and better protection activity (41.58%) against bacterial leaf blight of rice than that of thiodiazole copper and bismerthiazol (46.86 and 42.25%, respectively). Structure–activity relationship analysis exhibited that sulfone fragment favored inhibition. Overall, this study suggested that derivatives containing 1,3,4‐thiadiazole 3‐cyclopentylpropanamide can be used as new lead compounds for bactericide studies.     

Design,Synthesis and Antifungal Evaluation of N‐Substituted‐1‐(3‐chloropyridin‐2‐yl)‐N‐(pyridin‐4‐yl)‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxamide Derivatives

A series of 1‐(3‐chloropyridin‐2‐yl)‐5‐(trifluoromethyl)‐1H‐pyrazole‐4‐carboxamide derivatives which have di‐substituents on nitrogen were designed and synthesized. Bioassay results showed that all the synthetic compounds exhibited lower antifungal activities against Gibberella zeae, Cytospora mandshurica, and Fusarium oxysporum than T ₃ (14.7, 21.1, and 32.7 μg/mL), but some of them exhibited better activities against Botrytis cinerea, Phytophthora infestans, and Sclerotinia sclerotiorum than T ₃ (>200, >200, and >200 μg/mL); the EC₅₀ values of 7d and 7c against B. cinerea were 94.9 and 56.2 μg/mL, respectively. The EC₅₀ values of 7a , 7d , and 7c against S. sclerotiorum were 73.5, 78.7, and 68.5 μg/mL, respectively.     

Synthesis and Antibacterial Activity of Novel Substituted Purine Derivatives

A series of novel N‐substituted‐2‐(6‐morpholino‐9H‐purin‐9‐yl)acetamide and 4‐(9‐((5‐substituted‐1,3,4‐oxadiazole/thiadiazole‐2‐yl)methyl)‐9H‐purin‐6‐yl)‐morpholine derivatives were synthesized and evaluated their antibacterial activities against rice bacterial leaf blight and tobacco bacterial wilt caused by Xanthomonas oryzae pv. oryzae (Xoo) and Ralstonia solanacearum (R. solanacearum) via the turbidimeter test in vitro. Antibacterial bioassay indicated that most compounds demonstrated good inhibitory effect against Xoo and R. solanacearum. Especially, compound 6a demonstrated the best inhibitory effect against Xoo with half‐maximal effective concentration (EC₅₀) value of 8.39 μg/mL, which was even better than those of commercial agents Bismerthiazol and Thiodiazole copper. The synthesized purine derivatives containing amide and 1,3,4‐oxadiazole/thiadiazole moieties exhibited excellent antibacterial activities against Xanthomonas oryzae pv. oryzae and R. solanacearum in vitro.     

Synthesis and antimicrobial activities of novel quinazolin-4(3H)-one derivatives containing a 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moiety

A series of novel quinazolin-4(3H)-one derivatives (6a–6y) containing a 1,2,4-triazolo[3,4-b][1,3,4]thiadiazole moiety were designed and synthesized, and their structures were fully characterized by ¹H NMR, ¹³C NMR, HRMS and IR spectra. Among them, the structure of compound 6u was unambiguously confirmed via single crystal X-ray diffraction analysis. The obtained bioassay results showed that compounds 6h, 6k, 6l and 6y had the EC₅₀ (half-maximal effective concentration) values of 34.8, 28.2, 41.5 and 42.5 μg/mL against the phytopathogenic bacterium Xanthomonas oryzae pv. oryzae (Xoo), respectively, which were significantly better than commercial bactericide Bismerthiazol (EC₅₀ = 95.8 μg/mL). Additionally, compounds 6a and 6b exhibited the strong inhibition activity against the pathogen Xanthomonas axonopodis pv. citri (Xac).     

Design,Synthesis, and Bioactivity Evaluation of New Thiochromanone Derivatives Containing a Carboxamide Moiety

In this study, using the botanical active component thiochromanone as the lead compound, a total of 32 new thiochromanone derivatives containing a carboxamide moiety were designed and synthesized and their in vitro antibacterial activities against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were determined, as well as their in vitro antifungal activities against Botryosphaeria dothidea (B. dothidea), Phomopsis sp., and Botrytis cinerea (B. cinerea). Bioassay results demonstrated that some of the target compounds exhibited moderate to good in vitro antibacterial and antifungal activities. In particular, compound 4e revealed excellent in vitro antibacterial activity against Xoo, Xoc, and Xac, and its EC₅₀ values of 15, 19, and 23 μg/mL, respectively, were superior to those of Bismerthiazol and Thiodiazole copper. Meanwhile, compound 3b revealed moderate in vitro antifungal activity against B. dothidea at 50 μg/mL, and the inhibition rate reached 88%, which was even better than that of Pyrimethanil, however, lower than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing a carboxamide moiety.     

Design,synthesis and biological evaluation of novel 3-phenylpropanamide derivatives with acyl hydrazone units

In this study, a series of 3-phenylpropanamide derivatives with acyl hydrazone units were synthesized and characterized by ¹H NMR, ¹³C NMR and HR MS. And the structure of compound III₃₃ was confirmed by X-ray single crystal. The bioassay results showed that, compounds III₈, III₁₇, III₂₂, and III₃₄ showed excellent inhibition on Xanthomonas oryzae pv. pryzae (Xoo) with EC₅₀ values of 7.1, 8.8, 9.5, and 4.7 μg/mL in vitro. The EC₅₀ values of compounds III₁₂, III₁₄ and III₃₃ against Ralstonia solanacearum (Rs) were 7.6, 7.6 and 7.9 μg/mL, respectively, all lower than the values of thiadiazol copper (TC) was 66.8 μg/mL and bismerthiazol (BT) was 72.4 μg/mL. Compounds III₁₂, III₁₄, III₃₃, and III₃₄ exhibited excellent antibacterial activity of more than 80% against Xanthomonas axonopodis pv. citri (Xac) in vitro. Besides, compounds III₈ (51.4%) and III₃₄ (52.1%) were highly effective against Xoo in vivo, outperforming TC (49.5%) and BT (47.8%). Compounds III₈ (29.8%) and III₃₄ (24.6%) were close to TC (41.7%) and BT (47.8%) in terms of protective efficacy against Xoo in vivo. Meanwhile, some of title compounds also displayed inhibitory effects against phytopathogenic fungi. In a word, this study illustrated that the structures combined with phenylpropane amide derivatives of the acyl hydrazone units could be used as potential antibacterial reagents in the future.     

Synthesis and antibacterial activity of chalcone derivatives containing thioether triazole

The infection of Xanthomonas oryzae pv. Oryzae (Xoo), Ralstonia solanacearum (Rs), and Xanthomonas axonopodis pv. Citri (Xac) has become a major problem in agricultural production. In this study, a series of novel chalcone derivatives containing thioether triazoles were designed and synthesized. The structures of the novel compounds were systematically characterized via ¹H-NMR, ¹³C-NMR, and HRMS. Moreover, the antibacterial activity results showed that E₁₀, E₁₁, E₁₅, and E₁₆ have adequate antibacterial activities against Xoo, Rs, and Xac. Among the different compounds, E₁₅ exhibited remarkable inhibitory effect against Xac with an EC₅₀ of 9.1 μg.mL^-1, which was better than that of commercial agent bismerthiazol (54.9 μg.mL^-1). In addition, the possible antibacterial mechanism of the target compound E₁₅ against Xac was studied via scanning electron microscopy (SEM).     

Design,synthesis and antiviral activities of chalcone derivatives containing pyrimidine

A series of chalcone derivatives (T1-T23) containing pyrimidine were synthesized, characterized, and assessed for their antiviral activity against tobacco mosaic virus (TMV) activities. Most target compounds displayed better antiviral activities against TMV than commercial ningnanmycin. Among them, the EC₅₀ value of curative activities of compounds T1, T7, T9 and T19 (219.2, 228.2, 279.9 and 234.9 μg/mL, respectively) were superior to that of ningnanmycin (320.1 μg/mL). In addtion, the EC₅₀ value of protective activities of compounds T5, T9, T19 and T23 (235.0, 220.0, 199.5 and 187.2 μg/mL, respectively) were superior to that of ningnanmycin (307.4 μg/mL). Then, the antiviral mechanism of T19 and TMV coat protein (TMV-CP) was preliminarily investigated by microscale thermophoresis (MST) and molecular docking technology. The results showed that T19 had a strong binding affinity for TMV coat protein, and its dissociation constant (K_d) was 0.00310 ± 0.000916 μM, which was superior to ningnanmycin(0.165 ± 0.0799 μM). This study suggests that chalcone derivatives containing pyrimidine could be used as novel antiviral agents for controlling the plant viruses.     

Antiviral properties from plants of the Mediterranean flora

Natural products are a successful source in drug discovery, playing a significant role in maintaining human health. We investigated the in vitro cytotoxicity and antiviral activity of extracts from 18 traditionally used Mediterranean plants. Noteworthy antiviral activity was found in the extract obtained from the branches of Daphne gnidium L. against human immunodeficiency virus type-1 (EC₅₀ = 0.08 μg/mL) and coxsackievirus B5 (EC₅₀ = 0.10 μg/mL). Other relevant activities were found against BVDV, YFV, Sb-1, RSV and HSV-1. Interestingly, extracts from Artemisia arborescens L. and Rubus ulmifolius Schott, as well as those from D. gnidium L., showed activities against two different viruses. This extensive antiviral screening allowed us to identify attractive activities, offering opportunities to develop lead compounds with a great pharmaceutical potential.     

Synthesis of novel 2,3‐disubstituted quinazolin‐4(3H)‐one derivatives containing hydrazone skeleton as potent urease inhibitors and their antimicrobial activities

A new series of quinazolinones containing hydrazone moiety were synthesized, and their inhibitory activities on urease were assessed in vitro. Most of the compounds exhibited potent urease inhibitory activity. Among the synthesized compounds, molecule 4a bearing furan ring has the best inhibitory effect against urease with IC₅₀ = 2.90 ± 0.11 μg/mL. Compounds 4f , 4g , 4h , 4i , and 4j have hydroxy group on phenyl ring. Compound 4i is the most active inhibitor among these compounds with IC₅₀ = 5.01 ± 0.10 μg/mL, which has 3‐Cl and 4‐Br on phenyl ring. Also, newly synthesized compounds had been tested for their antimicrobial effects against three of Gram‐positive bacteria (Bacillus cereus 702 Roma, Staphylococcus aureus ATCC 25923, and Streptococcus pyogenes ATCC 19615) and three of Gram‐negative bacteria (Escherichia coli ATCC 25922, Proteus vulgaris ATCC 13315, and Pseudomonas aeruginosa ATCC 27853). Antimicrobial activity results show that compounds 4a , 4h , 4j , 4f , and 4l have the lowest minimum inhibitory concentration (MIC) value of 1000 μg/mL to all tested bacteria. The other compounds have the MIC value of >1000 μg/mL to all tested bacteria.     

Synthesis of novel 1,3,4-oxadiazole derivatives containing diamides as promising antibacterial and antiviral agents

In this paper, a variety of novel 1,3,4-oxadiazole derivatives possessing diamides were synthesized and tested for their antibacterial and antiviral activity. Preliminary antibacterial assays indicated that some intermediates and title compounds displayed excellent inhibition effects against plant pathogens Xanthomonas oryzae pv. oryzae (Xoo) and Xanthomonas axonopodis pv. citri (Xac). Further studies revealed that compound H15 exhibited the strongest activities against Xoo and Xac with minimal EC₅₀ values of 0.7 and 5.9 μg/mL, respectively. Antiviral bioassays suggested that some of these structures displayed appreciable curative activities and moderate protective effects against tobacco mosaic virus (TMV) in vivo. Among them, compound H8 exerted the best chemotherapeutic effect against TMV with the curative rate of 60.0% at 500 µg/mL, which was comparable with those of commercial agricultural antiviral agent ningnanmycin (54.2%). Given their significant biological activities, this kind of compound could serve as new leading compounds in the study of antibacterial and antiviral chemotherapy.     

Design,synthesis, and bioactivity evaluation of novel thiochromanone derivatives containing an oxime or oxime ether moiety

In this study, using botanical active component thiochromanone as the lead compound, a series of novel thiochromanone derivatives containing an oxime or oxime ether moiety were designed and synthesized. The half-maximal effective concentration (EC₅₀) values of compound 4a against Xanthomonas oryzae pv. oryzae (Xoo), Xanthomonas oryzae pv. oryzicolaby (Xoc), and Xanthomonas axonopodis pv. citri (Xac) were 6, 10, and 15 μg/ml, respectively, which were superior to those of Bismerthiazol and Thiodiazole-copper. Meanwhile, compound 4a also revealed better antifungal activity against Botrytis cinerea, with the EC₅₀ value of 18 μg/ml, than that of Carbendazim. To the best of our knowledge, this is the first report on the antibacterial and antifungal activities of this series of novel thiochromanone derivatives containing an oxime or oxime ether moiety.     

Novel 4(3H)‐Quinazolinone Derivatives Containing an Isoxazole Moiety: Design,Synthesis, and Bioactivity Evaluation

The aim of the present study is to design and synthesize a series of novel 4(3H )‐quinazolinone derivatives containing an isoxazole moiety and evaluate their antifungal activity against Gibberella zeae (G. zeae ), Fusarium oxysporum (F. oxysporum ), Cytospora mandshurica (C. mandshurica ), Phytophthora infestans (P. infestans ), and Pellicularia sasakii (P. sasakii ), and their antibacterial activity against Ralstonia solanacearum (R. solanacearum ) and Xanthomomu oryzae pv. oryzae (Xoo ). Bioassay results showed that the target compounds 8a–8o had certain antifungal activities against the test fungus at the concentration of 50 μg/mL, which were lower than those of Hymexazol and Epoxiconazole. Meanwhile, preliminary bioassay results showed that compounds 8a–8o had better antibacterial activity against R. solanacearum and Xoo at 200 and 100 μg/mL. In particular, compound 8i exhibited significant antibacterial activity against Xoo in vitro , with an inhibition rate of 100% at 200 μg/mL, which was superior to those of Bismerthiazol (72%) and Thiodiazole copper (35%).     

Antiviral and Antibacterial Activities of N‐(4‐Substituted phenyl) Acetamide Derivatives Bearing 1,3,4‐Oxadiazole Moiety

In this paper, a series of N‐(4‐substituted phenyl) acetamide derivatives bearing 1,3,4‐oxadiazole moiety were synthesised. Preliminary bioassays revealed that these compounds not only exhibited favourable antiviral activities toward tobacco mosaic virus (TMV) but also demonstrated sustained inhibition activities against plant pathogenic bacteria, including Xanthomonas oryzae pv. oryzae, Ralstonia solanacearum, and Xanthomonas axonopodis pv. citri. Among the derivatives, TC ₈ and TC ₂₀ exerted the strongest curative activities against TMV, with half‐maximal effective concentration (EC₅₀) values of 239.5 and 236.2 µg/mL, respectively, which were comparable to that of ningnanmycin (EC₅₀=273.2 µg/mL). Given their simple synthesis, the target compounds can serve as alternative antiviral candidates.     

Synthesis and fungicidal activity of novel 1,2,4-triazole derivatives containing a pyrimidine moiety

Abstract

A series of novel 1,2,4-triazole derivatives containing a pyrimidine moiety were synthesized and their fungicidal activities were evaluated. The preliminary biological test indicated that some of the target compounds exhibited moderate to good fungicidal activities against the tested plant pathogenic fungi compared with the commercial agent. Among them, compounds 9n and 9o exhibited excellent antifungal activity against Phompsis sp., with the half-maximal effective concentration (EC₅₀) values of 25.4 and 31.6?μg/mL, which were even better than the commercial agent of Pyrimethanil (32.1?μg/mL). Meanwhile, compound 9o showed better fungicidal activities against B. dothidea and B. cinerea with 40.1 and 55.1?μg/mL, respectively, in comparison with that of commercial Pyrimethanil (57.6 and 62.8?μg/mL).     

Design,Synthesis, and in vitro Anti‐mycobacterial Evaluation of Propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered (Thio)semicarbazone‐isatin‐moxifloxacin Hybrids

A new class of propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered (thio)semicarbazone‐isatin‐moxifloxacin hybrids 6a – h was designed, synthesized, and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H₃₇Rv and MDR‐TB as well as cytotoxicity in VERO cell line. All the synthesized hybrids (MIC: 0.05–2.0 μg/mL) exhibited excellent activities against M. tuberculosis H₃₇Rv and MDR‐TB; in particular, conjugate 6c (MIC: 0.05 and 0.12 μg/mL) was no inferior to the three references MXFX (MIC: 0.10 and 0.12 μg/mL), RIF (MIC: 0.39 and 32 μg/mL), and INH (MIC: 0.05 and >128 μg/mL) against the tested two strains. All hybrids (CC₅₀: 2–8 μg/mL) were much more cytotoxic than the parent MXFX (CC₅₀: 128 μg/mL) should be further optimized.     

Synthesis and Antiviral Bioactivity of Novel 2‐Substituted Methlthio‐5‐(4‐Amino‐2‐Methylpyrimidin‐5‐yl)‐1,3,4‐Thiadiazole Derivatives

A series of novel 2‐substituted methlthio‐5‐(4‐amino‐2‐methylpyrimidin‐5‐yl‐)‐1,3,4‐thiadiazole derivatives were synthesized, characterized and evaluated for antiviral activities against tobacco mosaic virus (TMV). The preliminary biological results indicated that most compounds exhibit excellent antiviral activity against TMV in vivo. Among these compounds, compounds 9c , 9i , and 9p displayed the similar curative effect against TMV (EC₅₀ = 287.05–322.47 µg/mL) to that of the commercial agent Ningnanmycin (EC₅₀ = 301.83 µg/mL). In particular, compound 9d demonstrated the best curative effect against TMV (EC₅₀ = 266.21 µg/mL), which was better than that of commercial Ningnanmycin.     

Ciprofloxacin‐isatin‐1H‐1,2,3‐triazole Hybrids: Design,Synthesis, and in vitro Anti‐tubercular Activity against M. tuberculosis

A new set of ciprofloxacin (CPFX)‐isatin‐1H‐1,2,3‐triazole hybrids 6a – l with greater lipophilicity compared with the parent CPFX was designed, synthesized, and assessed for their in vitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv as well as cytotoxicity in VERO cell line. The preliminary results showed that all hybrids (MIC: 0.39–50 μg/mL) exhibited promising activities against MTB H₃₇Rv, and six of them (MIC: 0.39–1.56 μg/mL) were more active than the parent CPFX (MIC: 3.12 μg/mL). In particular, the most active conjugate 6h (MIC: 0.39 μg/mL) was comparable with RIF (MIC: 0.39 μg/mL), and eight times more potent than CPFX. All conjugates (CC₅₀: 4–64 μg/mL) were more toxic than the parent (CC₅₀: 128 μg/mL) in VERO cell lines, and the most active hybrids, which also displayed the highest cytotoxicity, should be further optimized.