新型5-(对氯苯基)-3-(邻，对-二氯苯基)-4，5-二氢吡唑肟酯衍生物的合成，结构表征及抗菌活性

合成了10个未见文献报道的1-(5-(2-氯苯基)-3-(2,4-二氯苯基)-4,5-二氢-N-吡唑肟酯类衍生物,并经过元素分析、HRMS、核磁共振氢谱对其结构进行了表征。对新合成的化合物进行了初步抗Bacillus subtilis, Staphylococcus aureus, Escherichia coli 和 Pseudomonas aeruginosa生物活性测试,结果表明:化合物7c 和7f对供试病菌具有较好的体外杀灭活性,其MIC值达到1.562 μg/mL;化合物7c ,7d和7f 具有中等的抑制DNA回旋酶活性(IC₅₀ = 1.6~2.5 µg/mL)。在生物活性结果的基础上对系列化合物的构效关系进行了初步的探讨。     

Design,Synthesis, and In Vitro Anti‐mycobacterial Activities of Propylene‐Tethered Gatifloxacin‐Isatin Hybrids

A series of propylene‐tethered mono‐/bis‐isatin‐gatifloxacin hybrids 3a–f and 4a–f were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant tuberculosis (MDR‐TB) as well as cytotoxicity against VERO cell line. The results indicated that all hybrids exhibited promising anti‐mycobacterial activities against MTB H37Rv and MDR‐TB with MIC ranging from 0.25 to 16 μg/mL. In particular, the mono‐isatin‐gatifloxacin hybrid 3e (MIC: 0.25 and 0.25 μg/mL) was found to be most active against MTB H₃₇Rv and MDR‐TB strains, which was twofold more active than the parent gatifloxacin (MIC: 0.5 μg/mL) and comparable with rifampicin ( RIF ) (MIC: 0.25 μg/mL) against MTB H₃₇Rv, and 4‐ > 512 times more potent than the three references gatifloxacin (MIC: 1.0 μg/mL), RIF (MIC: 64 μg/mL), and isoniazid (>128 μg/mL) against MDR‐TB, could act as a starting point for further optimization.     

Design,Synthesis, and in vitro Anti‐mycobacterial Activities of Propylene‐tethered Heteronuclear Bis‐isatin Derivatives

A series of novel propylene‐tethered heteronuclear bis‐isatin derivatives were designed, synthesized, and assessed for their in vitro and anti‐mycobacterial activities. All hybrids exhibited considerable antibacterial and anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multi‐drug‐resistant tuberculosis (MDR‐TB) with minimum inhibitory concentration (MIC) ranging from 16 to 256 μg/mL. In particular, the heteronuclear bis‐isatin 4i (MIC: 25 and 16 μg/mL) was most active against M. tuberculosis H₃₇Rv and MDR‐TB strains, which was fourfold and greater than eightfold more potent than the first‐line anti‐tubercular agents rifampicin (MIC: 64 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, could act as a lead for further optimization.     

Efficient Synthesis of Novel 3‐Phenyl‐5‐thioxo‐3,4,5,6‐tetrahydroimidazo[4,5‐c]pyrazole‐2(1H)‐carbothioamide Derivatives Using a CeO2–MgO Catalyst and Evaluation of Antimicrobial Activity

Imidazo[4,5‐c ]pyrazole derivatives ( 3a–f , 4a–f , and 5a–f ) were efficiently synthesized by one‐pot three‐component reactions using CeO₂–MgO as the catalyst. The synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, and mass spectroscopic analyses. The in vitro antimicrobial activity of the synthesized compounds against various bacterial and fungal strains was screened. Compound 3b was highly active [minimum inhibitory concentration (MIC): 0.5 μg/mL] against Gram‐positive Staphylococcus aureus , and compounds 3b , 3f , 4d , and 4e were highly active (MIC: 0.5, 2, 2, and 0.5 μg/mL, respectively) against Gram‐negative Pseudomonas aeruginosa and Klebsiella pneumoniae , relative to standard ciprofloxacin in the antibacterial activity screening. Compounds 3b and 4f were highly active (MIC: 4 and 0.5 μg/mL, respectively) against Aspergillus fumigatus and Microsporum audouinii in the antifungal activity screening compared with the clotrimazole standard.     

1H‐1,2,3‐triazole‐tethered 8‐OMe Ciprofloxacin and Isatin Hybrids: Design,Synthesis and in vitro Anti‐mycobacterial Activities

A new class of 1H ‐1,2,3‐triazole‐tethered 8‐OMe ciprofloxacin (8‐OMe CPFX) isatin hybrids 5a–l was designed, synthesized and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H₃₇Rv and multi‐drug‐resistant tuberculosis (MDR‐TB). All targets (minimum inhibitory concentration (MIC): 0.20–8.0 μg/mL) exhibited promising inhibitory activity against MTB H₃₇Rv and MDR‐TB. Among them, conjugate 5h (MIC: 0.20 μg/mL), was 2–16 times more potent in vitro than the references CPFX (MIC: 3.12 μg/mL), 8‐OMe CPFX (MIC: 1.56 μg/mL) and RIF (MIC: 0.39 μg/mL) against MTB H₃₇Rv. The most potent hybrid 5l (MIC: 0.25 μg/mL) was 8–256 times more active than the three references (MIC: 2.0–64 μg/mL) against MDR‐TB. Both of them warrant further investigations.     

Tetraethylene Glycol Tethered Heteronuclear Bis‐isatin Derivatives: Design,Synthesis, and In Vitro Anti‐mycobacterial Activities

A series of novel tetraethylene glycol tethered heteronuclear bis‐isatin derivatives 7a – l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis (MTB) H37Rv and multidrug‐resistant TB (MDR‐TB) as well as cytotoxicity in VERO cell line. All hybrids exhibited potential anti‐mycobacterial activities against MTB H37Rv and MDR‐TB, and acceptable cytotoxicity. Among them, the heteronuclear bis‐isatin 7l [minimum inhibitory concentration (MIC): 16 and 16 μg/mL] was found to be most active against MTB H37Rv and MDR‐TB strains, which was 2‐fold and >8‐fold, respectively, more potent than were the first‐line anti‐tubercular agents rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, also demonstrated acceptable cytotoxicity profile (CC₅₀: 62.5 μg/mL), could act as a starting point for further optimization.     

Design,Synthesis, and In Vitro Anti‐mycobacterial Evaluation 1H‐1,2,3‐triazole‐tethered Ciprofloxacin and Isatin Conjugates

Eight novel 1H‐1,2,3‐triazole‐tethered ciprofloxacin (CPFX) isatin conjugates 5a – h with greater lipophilicity compared with CPFX were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activity against Mycobacterium smegmatis and Mycobacterium tuberculosis (MTB) H₃₇Rv. The preliminary results showed that all hybrids (MIC: 12.5–100 μg/mL) exhibited considerable activity against M. smegmatis , but less active than the parent CPFX (MIC: 6.25 μg/mL) and the reference INH (MIC: 0.78 μg/mL). Against MTB H₃₇Rv, all hybrids displayed excellent inhibitory activity with MICs ranging from 1.56 to 25 μg/mL, particularly, 5h (MIC: 1.56 μg/mL) was twofold more active CPFX (MIC: 3.12 μg/mL), warrant further investigations.     

Synthesis and Antimicrobial Activity of Novel 2‐Substituted Phenoxy‐N‐(4‐substituted Phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl)acetamide Derivatives

A series of 2‐substituted phenoxy‐N‐(4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazole‐2‐yl)acetamide derivatives 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h , 8i , 8j , 8k , 8l , 8m , 8n , 8o , 8p , 8q , 8r , 8s , 8t was synthesized by the reaction of phenoxyacetyl chloride 7 with intermediate 4‐substituted phenyl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐amine 5 . Their structures were confirmed by ¹H NMR, ¹³C NMR, MS, IR, and elemental analyses. The synthesized compounds were also screened for their antimicrobial activity against three types of plant fungi (Gibberella zeae , Phytophthora infestans , and Paralepetopsis sasakii ) and two kinds of bacteria [Xanthomonas oryzae pv. oryzae (Xoo ) and Xanthomonas axonopodis pv. citri (Xac )] showing promising results. In particular, 8b , 8f , 8g , and 8h exhibited excellent antibacterial activity against Xoo , with 50% effective concentration (EC₅₀) values of 35.2, 80.1, 62.5, and 82.1 µg/mL, respectively, which are superior to the commercial antibacterial agent bismerthiazol (89.9 µg/mL). The preliminary structure–activity relationship studies of these compounds are also briefly described.     

Design,Synthesis, and Herbicidal Activities of 3‐Aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles

In order to find novel bleaching herbicide lead compounds, a series of novel 3‐aryl‐4‐substituted‐5‐[3‐(trifluoromethyl)phenoxy]‐1,2,4‐triazoles were designed and synthesized by the multi‐step reactions. N‐(Arylformamido)phenylthioureas undergo ring closure in the presence of sodium hydroxide to generate 3‐aryl‐4‐substituted‐4H‐[1,2,4]triazol‐5‐thiols 1 , which reacted with methyl sulfate in the presence of K₂CO₃ to give 3‐aryl‐5‐methylsulfanyl‐4‐substituted‐4H‐[1,2,4]triazoles 2 . The target compounds 4 were synthesized by the oxidation of 2 in the presence of H₂O₂ and Na₂WO₄, followed by the substitution with 3‐(trifluoromethyl)phenol in moderate to good yields. Their structures were confirmed by IR, ¹H NMR, EI–MS, and elemental analyses. The preliminary bioassay indicated that some of them displayed moderate to good selective herbicidal activity against Brassica campestris L at the concentration of 100 µg/mL. Compounds 4c and 4i possessed 75.0% and 82.6% inhibition against Brassica campestris L at the concentration of 100 µg/mL. However, the target compounds 4 showed weak herbicidal activity against Echinochloa crus‐galli at the concentration of 100 and 10 µg/mL.     

Design,Synthesis and In Vitro Anti‐mycobacterial Activity of Propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered Isatin‐moxifloxacin Hybrids

Ten propylene‐1H‐1,2,3‐triazole‐4‐methylene‐tethered isatin‐moxifloxacin hybrids 5a–j were synthesized via Cu‐promoted azide‐alkyne cycloaddition reaction, and screened for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H₃₇Rv and multidrug‐resistant tuberculosis. The results showed that all the synthesized hybrids [minimum inhibitory concentration (MIC): 0.25–4.0 μg/mL] displayed considerable activities against the tested two strains, but all less active than the parent moxifloxacin (MIC: 0.10 and 0.12 μg/mL). The resistance index of the most targets was around 1, suggesting this kind of hybrids could reduce the cross–resistance to some extent. Among them, hybrid 5 g was found most active against Mycobacterium tuberculosis H₃₇Rv with MIC of 0.39 μg/mL, which was comparable with rifampicin (MIC: 0.39 μg/mL), while conjugate 5a (MIC: 0.25 μg/mL) was 128– > 512 times more active than rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against multidrug‐resistant tuberculosis.     

Isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin Hybrids: Design,Synthesis, and in vitro Anti‐mycobacterial Evaluation

Isatin and coumarin derivatives with potential anti‐tubercular activity, while (thio)semicarbazide/oxime and 1H‐1,2,3‐triazole moieties exhibited favorable properties such as hydrogen bonding and/or metal chelation capability, so integration of the four pharmacophores into one molecule may provide more effective anti‐tubercular candidates. Based on the consideration earlier, 12 isatin‐(thio)semicarbazide/oxime‐1H‐1,2,3‐triazole‐coumarin hybrids 8a–l were designed, synthesized, and evaluated for their in vitro anti‐mycobacterial activities against M. tuberculosis (MTB) H₃₇Rv and MDR‐TB. The results showed that all the hybrids (MIC: 50–>200 μg/mL) exhibited weak to moderate inhibitory activity against MTB H₃₇Rv and MDR‐TB, which were far less potent than the references isoniazid (MIC: 0.05 μg/mL) and rifampicin (MIC: 0.39 μg/mL) against MTB H₃₇Rv. The most active hybrid 8h (MIC: 50 μg/mL) was comparable with rifampicin (MIC: 32 μg/mL) and more active than isoniazid (MIC: >128 μg/mL) against MDR‐TB, could be act as a lead for further optimization. Moreover, the enriched structure–activity relationship paved the way to the further rational development of this kind of hybrids.     

Synthesis and Fungicidal Activity of (E)‐5‐[1‐(2‐Oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐4‐one Derivatives

The novel fungicidal agents, (E )‐5‐[1‐(2‐oxo‐1‐oxaspiro[4,5]dec/non‐3‐en‐3‐yl)ethylidene]‐2‐aminoimidazolin‐ 4‐one derivatives, were designed and synthesized in moderate to excellent yields in four steps using α ‐hydroxyketone and diketene as raw materials and characterized by HR‐ESI‐MS , ¹H NMR and X‐ray diffraction. The preliminary bioassay showed that some of these compounds, such as 5e , 6a , 6e , and 7 h exhibit 87.8%, 91.3%, 89.9% and 87.8% inhibition rates against Sclerotinia scleotiorum , 3b , 3c , 4c and 7 h exhibit 96.4%, 92.5%, 90.3% and 76.9% inhibition rates against Phytophthora capsici at the concentration of 50 µg/mL , respectively. These compounds exhibited significant fungicidal activities against S. scleotiorum and P. capsici with EC₅₀ values of 2.56–11.60 µg/mL , and compounds 6e and 7 h exhibited weak inhibition against the spore germination of S. scleotiorum , while the spore germination of P. capsici was strongly inhibited by compound 7 h solution. Scanning electron microscopy (SEM ) and transmission electron microscopy (TEM ) observation indicated that compound 7 h had a significant impact on the structure and function of the hyphal cell wall of P. capsici mycelium.     

Heteronuclear 5‐Fluoroisatin Dimers: Design,Synthesis, and Evaluation of Their In Vitro Anti‐mycobacterial Activities

A series of novel heteronuclear 5‐fluoroisatin dimers 4a–j tethered through ethylene were designed, synthesized, and examined for their in vitro anti‐mycobacterial activities against Mycobacterium tuberculosis H37Rv and multi‐drug resistant tuberculosis (MDR‐TB). All hybrids exhibited potential anti‐mycobacterial activities against the tested two strains with minimum inhibitory concentration (MIC) in a range of 25 to 256 μg/mL. In particular, the heteronuclear 5‐fluoroisatin dimer 4a (MIC: 25 and 32 μg/mL) was most active against Mycobacterium tuberculosis H37Rv and MDR‐TB strains, which was twofold and greater than fourfold more potent than rifampicin (MIC: 64 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐TB, warrant further optimization.     

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.     

Guanidinylated Amphiphilic Polycarbonates with Enhanced Antimicrobial Activity by Extending the Length of the Spacer Arm and Micelle Self‐Assembly

Nine guanidinylated amphiphilic polycarbonates are rationally designed and synthesized. Each polymer has the same biodegradable backbone but different side groups. The influence of the hydrophobic/hydrophilic effect on antimicrobial activities and cytotoxicity is systematically investigated. The results verify that tuning the length of the spacer arm between the cationic guanidine group and the polycarbonate backbone is an efficient design strategy to alter the hydrophobic/hydrophilic balance without changing the cationic charge density. A spacer arm of six methylene units (CH₂)₆ shows the best antimicrobial activity (minimum inhibitory concentration, MIC = 40 µg mL^?1 against Escherichia coli, MIC = 20 µg mL^?1 against Staphylococcus aureus, MIC = 40 µg mL^?1 against Candida albicans) with low hemolytic activity (HC₅₀ > 2560 µg mL^?1). Furthermore, the guanidinylated polycarbonates exhibit the ability to self‐assemble and present micelle‐like nanostructure due to their intrinsic amphiphilic macromolecular structure. Transmission electron microscopy and dynamic light scattering measurements confirm polymer micelle formation in aqueous solution with sizes ranging from 82 to 288 nm.     

Synthesis and Bioactivities of Novel 1‐(3‐Chloropyridin‐2‐yl)‐N‐Substituted‐5‐(Trifluoromethyl)‐Pyrazole Carboxamide Derivatives

A series of novel 1‐(3‐chloropyridin‐2‐yl)‐N‐substituted‐5‐(trifluoromethyl)‐pyrazole carboxamide derivatives TC₁ , TC₂ , TC₃ , TC₄ , TC₅ , TC₆ , TC₇ , TC₈ , TC₉ , TC₁₀ , TC₁₁ were synthesized and characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analysis. All the target compounds were tested in vitro for their antibacterial activities and antifungal activities. The preliminary bioassays indicated that compound TC₆ exhibited excellent activity against Xanthomonas oryzae (94.9% and 84.9%) at different concentrations (200 µg/mL and 100 µg/mL), which was higher than that of Bismerthiazol (94.6% and 64.0%), respectively. At the same time, most of the compounds exhibited moderate antifungal activities against four kinds of phytopathogenic fungi     

Synthesis,in vitro Antimicrobial,and Cytotoxic Activities of New 1,3,4‐Oxadiazin‐5(6H)‐one Derivatives from Dehydroabietic Acid

A series of new 1,3,4‐oxadiazin‐5(6H)‐one derivatives ( 6a–n ) of dehydroabietic acid were designed and synthesized as potential antimicrobial and antitumor agents. Their structures were characterized by IR, ¹H NMR, ¹³C NMR, MS, and elemental analyses. All the title compounds were evaluated for their antimicrobial activity against four bacterial and three fungal strains using the serial dilution method. Among them, compound 6e showed the highest antibacterial activity against Bacillus subtilis with a minimum inhibitory concentration (MIC) value of 1.9 μg/mL. In addition, the in vitro cytotoxic activities of the title compounds were also assayed against three human carcinoma cell lines (MCF‐7, SMMC‐7721, and HeLa) through the MTT colorimetric method. As a result, compounds 6b , 6g , 6k, and 6m exhibited significant inhibition against at least one cell line with IC₅₀ values below 10 μM. Compound 6m was especially found to be the most potent derivative with IC₅₀ values of 2.26 ± 0.23, 0.97 ± 0.11, and 1.89 ± 0.31 μM against MCF‐7, SMMC‐7721, and HeLa cells, respectively, comparable to positive control etoposide.     

Synthesis and Bioactivities of Novel N‐(4‐(2‐Aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamides

A series of novel N‐(4‐(2‐aryloxythiazol‐5‐yl)but‐3‐yn‐2‐yl)benzamide derivatives were designed and synthesized. Their structures were identified by ¹H NMR and elemental analyses. Preliminary bioassays indicated that some title compounds provided >80% control of Sclerotinia sclerotiorum at 50 µg/mL and >70% herbicidal activities against B. campestris at 100 µg/mL. Their structure‐activities relationships were also discussed.     

Design,Synthesis, and In Vitro Anti‐mycobacterial Activities of Propylene Tethered Benzofuran–Isatin Hybrids

A series of novel propylene tethered benzofuran–isatin hybrids 5a–j were designed, synthesized, and assessed for their in vitro anti‐mycobacterial activity against Mycobacterium tuberculosis (MTB) H₃₇Rv and multidrug‐resistant (MDR)‐MTB strains. All hybrids exhibited promising anti‐mycobacterial activities against the tested two pathogens with minimum inhibitory concentration (MIC) ranging from 2 to 32 μg/mL, and the resistance index for a significant part of the hybrids was ≤1, indicating their potential for the treatment of drug‐resistant tuberculosis. Hybrid 5g (MIC: 2 and 4 μg/mL) was found to be the most active against MTB H₃₇Rv and MDR‐MTB, which was eightfold and >32‐fold more active than the first‐line anti‐tuberculosis drugs rifampicin (MIC: 32 μg/mL) and isoniazid (MIC: >128 μg/mL) against MDR‐MTB, and it could act as a starting point for further optimization.