Synthesis,Antiproliferative Evaluation,and Molecular Docking Study of Novel Longifolene-Derived Tetraline Fused Thiazole-Amide Derivatives

Twenty novel longifolene-derived tetraline fused thiazole-amide compounds were synthesized from longifolene, a renewable natural resource. Their structures were characterized by FT-IR, NMR, ESI-MS, and elemental analysis. The in vitro antiproliferative activity of these compounds against SK-OV-3 ovarian cancer cell lines, MCF-7 human breast cancer cell lines, HepG2 human liver cancer cell lines, A549 human lung adenocarcinoma cell lines, and T-24 human bladder cancer cell lines was tested by MTT assay. Compounds 6a – 6c displayed significant and broad-spectrum antiproliferative activity against almost the tested cancer cell lines with IC₅₀ in the range of 7.84 to 55.88 μM, of which compound 6c exhibited excellent antiproliferative activities with 7.84 μM IC₅₀ against SKOV-3, 13.68 μM IC₅₀ against HepG2, 15.69 μM IC₅₀ against A549, 19.13 μM IC₅₀ against MCF-7, and 22.05 μM IC₅₀ against T-24, showing better and broad-spectrum antiproliferative effect than that of the positive control 5-FU. Furthermore, the action model was analyzed by the molecular docking study. Some intriguing structure-activity relationships were found and discussed herein by DFT theoretical calculation.     

Novel Thioether-Bridged 2,6-Disubstituted and 2,5,6-Trisubstituted Imidazothiadiazole Analogues: Synthesis,Antiproliferative Activity,ADME, and Molecular Docking Studies

In this study, starting from 2-amino-1,3,4-thiadiazole derivatives ( 3 – 5 ), a new series of 2,6-disubstituted (compounds 7 – 15 ) and 2,5,6-trisubstituted (compounds 16 – 33 ) imidazo[2,1-b][1,3,4]-thiadiazole derivatives were synthesized using cyclization and Mannich reaction mechanisms, respectively. All synthesized compounds were characterized by ¹H-NMR, ¹³C-NMR, FT-IR, elemental analysis, and mass spectroscopy techniques. Also, X-ray diffraction analysis were used for compounds 4 , 7 , 11 , 17 , and 19 . The cytotoxic effects of the new compounds on the viability of colon cancer cells (DLD-1), lung cancer cells (A549), and liver cancer cells (HepG2) were investigated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method in vitro. Compound 15 was found to be the most potent anticancer drug candidate in this series with an IC₅₀ value of 3.63 μM against HepG2 for 48 h. Moreover, the absorption, distribution, metabolism, and excretion (ADME) parameters of the synthesized compounds were calculated and thus, their potential to be safe drugs was evaluated. Finally, to support the biological activity experiments, molecular docking studies of these compounds were carried out on three different target cancer protein structures (PDB IDs: 5ETY, 1M17, and 3GCW), and the amino acids that play key roles in the binding of the compounds to these proteins were determined.     

Design,Synthesis, Insecticidal Activities and Molecular Docking of Sulfonamide Derivatives Containing Propargyloxy or Pyridine Groups

The discovery of new highly active molecules from natural products is a common method to create new pesticides. Celangulin V targeting Mythimna separate (M. separate) midgut V-ATPase H subunit, has received considerable attention for its excellent insecticidal activity and unique mechanism of action. Therefore, combined with our preliminary work, thirty-seven sulfonamide derivatives bearing propargyloxy or pyridine groups were systematically synthesized to search for insecticidal candidate compounds with low cost and high efficiency on the H subunit of V-ATPase. Bioactive results showed that compounds A2-A4 and A6-A7 exhibited a better bioactivity with median effective concentration (LC₅₀) values (2.78, 3.11, 3.34, 3.54 and 2.48 mg/mL, respectively) against third-instar larvae of M. separate than Celangulin V (LC₅₀=18.1 mg/mL). Additionally, molecular docking experiments indicated that these molecules may act on the H subunit of V-ATPase. Based on the above results, these compounds provide new ideas for the discovery of insecticides.     

Synthesis,Antioxidant and Antiproliferative Evaluation,Molecular Docking and DFT Studies of Some Novel Coumarin and Fused Coumarin Derivatives

N′-[(4-Chloro-2-oxo-2H-chromen-3-yl)methylene]-2-cyanoacetohydrazide ( 3 ) was synthesized in excellent yield from the condensation of 4-Chloro-2-oxo-2H-chromene-3-carbaldehyde with cyanoacetohydrazide. Compound 3 was utilized as a building block to synthesize novel coumarin and heterocycle-fused coumarin derivatives. The chemical structures of all the new coumarin compounds were identified by spectral analyses. Some of the new coumarins compounds were screened in human cancer cell lines (HEPG-2, MCF-7, HCT-116 and PC-3) to learn about their cytotoxic effects in addition to the study of their DNA damage and antioxidant activity. Three of these compounds exhibited remarkable antioxidant and anti-proliferative activities. Moreover, they have the capability to protect DNA from damage induced by bleomycin. Molecular docking, DFT and molecular electrostatic potential studies were performed on the compounds in vitro.     

Design,Synthesis, Cytotoxic Screening and Molecular Docking Studies of Novel Hybrid Thiosemicarbazone Derivatives as Anticancer Agents

Thiosemicarbazones have been the focus of scientists owing to their broad clinical anticancer range. Herein, A Series of new thiosemicarbazone derivatives 5 – 9 were synthesized and confirmed through the use of different spectroscopic techniques along with elemental analysis. The in vitro cytotoxic activity of compounds 5 – 9 against MCF-7 and A549 cell lines and normal breast cells were assessed. Several compounds were found to be active. The most active compound 7 caused MCF-7 cell cycle arrest at G1/ S phases; and induced apoptosis at the pre-G1 phase. The apoptosis-inducing activity of compound 7 was proofed by the elevation of caspase 3/7 activity and also by up-regulation of the expression of Bax and p53 proteins together with the down-regulation of the expression of the Bcl-2 protein. It also had a strong inhibitory effect topoisomerase IIβ enzyme. Molecular Docking study revealed that the synthesized compounds had good docking scores compared to the standard drug Etoposide towards the topoisomerase IIβ protein (3QX3). Overall, these findings confirmed that the new thiosemicarbazone derivatives could aid in the development of promising cancer drug candidates.     

Design,Synthesis and Molecular Docking Studies of Some Tetrahydropyrimidine Derivatives as Possible Fascin Inhibitors

Eight derivatives of tetrahydropyrimidine scaffold were designed and prepared as hybrid compounds possessing the structural features of both monastrol as an anticancer drug and nifedipine as a fascin blocking agent. All of the compounds were evaluated for their cytotoxic potency and the ability to inhibit 4T1 breast cancer cells migration. Then, they were investigated in silico for their ability to inhibit the fascin protein using molecular docking simulation. The most potent compound was 4d and the weakest one was 4a according to the in vitro cytotoxicity assay. The corresponding IC₅₀ values were 193.70 and 248.75 μm , respectively. The least cytotoxic compound ( 4a ) was one of the strongest ones in binding to the fascin binding site according to the molecular docking results. 4a and 4e inhibited the 4T1 cells migration better than other compounds. They were more potent than nifedipine in inhibiting the migration process. In silico studies proved 4h to be the most potent fascin inhibitor in terms of ΔG_bind although it was not inhibiting migration. The controversy between the in vitro and in silico results may cancel the theory of the involvement of the fascin inhibition in the migration inhibition. However, the considerable antimigratory effects of some of the synthesized compounds encourage performing further in vivo experiments to introduce novel tumor metastasis inhibitors.     

Targeting Colon Cancer Cells with Pyrazino-Imidazolinone Derivatives: Synthesis,Molecular Docking,and in Vitro Evaluation of Anti-Proliferative and Pro-Apoptotic Activities

We report the synthesis, spectroscopic characterization, molecular docking and biological evaluation of nine pyrazino-imidazolinone derivatives. These derivatives were evaluated for their anticancer activity against three cancer cell lines: 518A2 melanoma, HCT-116, and HCT-116 p53 knockout mutant colon carcinoma. The MTT assay was employed to assess their effectiveness. Among the nine compounds tested, four compounds (5 a, 5 d, 5 g, and 5 h) exhibited promising antiproliferative activity specifically against HCT-116 p53-negative cells (IC₅₀ 0.23, 0.20, 2.07 and 58.75 μM, respectively). Interestingly, treatment with the 3,4-dimethoxyphenyl derivative 5a resulted in a significant increase (199 %) in caspase activity in HCT-116 p53-negative cells compared to untreated cells while the bromo-pyrazine derivative 5d demonstrated (190 %) increase. These findings suggest that compounds 5a and 5 d induce p53-independent apoptotic cell death. Additionally, in silico molecular docking studies with EGFR and tyrosinase proteins indicated that compounds 5 d and 5 e have the potential to bind to important anticancer drug targets.     

Synthesis,Characterization, and Biological Study of 3-Trifluoromethylpyrazole Tethered Chalcone-Pyrrole and Pyrazoline-Pyrrole Derivatives

The present study illustrates the design and synthesis of new series of 3-trifluoromethylpyrazole tethered chalcone-pyrrole and pyrazoline-pyrrole derivatives. All compounds were further screened for in vitro cytostatic activities on full NCI 60 cancer cell lines at National Cancer Institute, USA. Compounds (2E)-3-(1H-pyrrol-2-yl)-1-{4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}prop-2-en-1-one ( 5a ) and (2E)-1-{3-methyl-4-[3-(trifluoromethyl)-1H-pyrazol-1-yl]phenyl}-3-(1H-pyrrol-2-yl)prop-2-en-1-one ( 5c ) displayed significant antiproliferative activity (Growth Percentage: −77.10 and −92.13, respectively at 10 μM concentration) against the UO-31 cell lines from renal cancer and were further selected for assay at 10-fold dilutions of five different concentrations (10⁻⁴ to 10⁻⁸ M). Both compounds 5a and 5c exhibited promising antiproliferative activity (GI₅₀: 1.36 to 0.27 μM) against leukemia cancer cell lines HL-60 and RPMI-8226, colon cancer cell lines KM-12; breast cancer cell lines BT-549. Moreover, both compounds 5a and 5c were found to be non-cytotoxic (LC₅₀>100) against HL-60, RPMI-8226, and KM-12 cell lines. Remarkably, GI₅₀ values of compounds 5a and 5c were identified as more promising than sunitinib against most cancer cell lines. In silico study of compounds 5a and 5c exemplified the desired ADME properties for drug-likeness as well as tighter interactions with VEGFR-2. Hence, compounds 5a and 5c would be good cytotoxic agents after further clinical study.     

Antimicrobial,Antiproliferative Effects and Docking Studies of Methoxy Group Enriched Coumarin-Chalcone Hybrids

Methoxy group enriched eight coumarin-chalcone hybrid derivatives were synthesized. Antimicrobial/ antiproliferative activities were tested against eight human pathogenic microorganisms and four cancer cell lines (AGS, HepG2, MCF-7 and PC-3), respectively. Antimicrobial results showed that most of the compounds were almost more active than used standard antibiotics. Cytotoxicity results showed that 2,3,4-trimethoxyphenyl and thiophene containing structures have promising antiproliferative effects against AGS gastric cell lines with ∼5 μg/ml IC₅₀ values. At the same time, 2,4-dimethoxyphenyl bearing derivative exhibited the lowest IC₅₀ values against HepG2 (∼10 μg/ml) and PC-3 (∼5 μg/ml) cell lines. Particularly, the cell viabilities of MCF-7 cell lines were remarkably inhibited by all the compounds with lower IC₅₀ values. Therefore, molecular docking studies between hybrid ligands and quinone reductase-2 enzyme (regulates in MCF-7 cancer cells) were performed. The results demonstrated that all the derivatives can smoothly interact with interested enzyme in agreement with the experimental results. Finally, ADME parameters were studied to reveal drug-likeness potentials of the coumarin-chalcone hybrids.     

新型2-喹诺酮类Polo样激酶1抑制剂的设计合成及分子对接研究

目的:设计合成新型2-喹诺酮类Polo样激酶1(Plk1)抑制剂。方法:以Plk1抑制剂ON 01910为先导化合物,利用生物电子等排原理设计一系列2-喹诺酮类衍生物,用Autodock软件将该类化合物与Plk1进行分子对接和虚拟筛选,计算结合自由能;以取代的氯(溴)苄为起始原料,先后经巯基乙酸取代、双氧水氧化、与(对甲氧基)苯胺酰化,再经环合、水解制得目标化合物。结果:设计的化合物大多数与Plk1的结合自由能均比ON 01910的低,结合强度高、稳定性好;合成了16个2-喹诺酮类衍生物,产物结构经1H-NMR确证。结论:所得化合物中有15个为新化合物,化合物的结构设计科学合理,虚拟筛选结果良好,为后续实体筛选和化合物结构优化提供了理论依据和参考。     

Molecular Design,Synthesis and Docking Study of Alkyl and Benzyl Derivatives of Robustic Acid as Topoisomerase I Inhibitors

Robustic acid is reported to be a bioactive compound, isolated from the medicinal plant Dalbergia benthamii Prain . Ten alkyl and benzyl derivatives ( 2a – 2j ) of robustic acid were designed and synthesized based on molecular docking approaches. The biological activities of most of the synthesized compounds (such as 2g , 2h , and 2i ) were closely consistent with the docking results. In particular, 4‐O‐phenylpropyl substituted compound 2g displayed potent topoisomerase I inhibitory activity as well as cytotoxicity against SMMC‐7721, HepG2, and HeLa cell lines. Further biological testing suggests that compound 2g acted mainly by an arrest of the tumor cells in G1 phase of the cell cycle and suppressed cell proliferation by inducing apoptosis. The findings of this study are encouraging with respect to potential utilization of these compounds as new topoisomerase I inhibitors.     

Design and Construction of Aroyl‐Hydrazone Derivatives: Synthesis,Crystal Structure,Molecular Docking and Their Biological Activities

Here, we report the synthesis and characterization of four new aroyl‐hydrazone derivatives L₁ – L₄ , and their structural as well as biological activities have been explored. In addition to docking with bovine serum albumin (BSA) and duplex DNA, the experimental results demonstrate the effective binding of L₁ – L₄ with BSA protein and calf thymus DNA (ct‐DNA) which is in agreement with the docking results. Further biological activities of L₁ – L₄ have been examined through molecular docking with different proteins which are involved in the propagation of viral or cancer diseases. L₁ shows best binding affinity with influenza A virus polymerase PB2 subunit (2VY7) with binding energy ?11.42 kcal/mol and inhibition constant 4.23 nm , whereas L₂ strongly bind with the hepatitis C virus NS5B polymerase (2WCX) with binding energy ?10.47 kcal/mol and inhibition constant 21.06 nm . Ligand L₃ binds strongly with TGF‐beta receptor 1 (3FAA) and L₄ with cancer‐related EphA2 protein kinases (1MQB) with binding energy ?10.61 kcal/mol, ?10.02 kcal/mol and inhibition constant 16.67 nm and 45.41 nm , respectively. The binding energies of L₁ – L₄ are comparable with binding energies of their proven inhibitors. L₁ , L₃ and L₄ can be considered as both 3FAA and 1MQB dual targeting anticancer agents, while L₁ and L₃ are both 2VY7 and 2WCX dual targeting antiviral agents. On the other side, L₂ and L₄ target only one virus related target (2WCX). Furthermore, the geometry optimizations of L₁ – L₄ were performed via density functional theory (DFT). Moreover, all four ligands ( L₁ – L₄ ) were characterized by NMR, FT‐IR, ESI‐MS, elemental analysis and their molecular structures were validated by single crystal X‐ray diffraction studies.     

Design,Synthesis, and Biological Evaluation of Dexibuprofen Derivatives as Novel Anti-Inflammatory,Antioxidant and Molecular Docking Studies

Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, ¹H-NMR, and ¹³C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC₅₀=19.8 μM), DR9 (IC₅₀=24.8 μM) and DR3 (IC₅₀=47.2 μM) as compared with Dexibuprofen (IC₅₀=156.6 μM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %).     

Antimicrobial Pyridazines: Synthesis,Characterization, Cytotoxicity,Substrate Promiscuity,and Molecular Docking

A facile and convenient synthesis of new pyridazines suitable for use as antimicrobial agents was reported. The hydrazide intermediate was coupled with various benzaldehydes and/or acetophenones and cyclized instantaneously to afford target pyridazine derivatives. The structures of new pyridazines were confirmed by IR, ¹H‐ and ¹³C‐NMR, elemental analysis in addition to representative LC/MS. Antimicrobial activity was screened against 10 bacterial and fungal strains. The new pyridazines showed strong to very strong antibacterial activity against Gram‐negative (GNB) bacteria, while none of them showed significant antifungal activity at the same concentration range. Chloro derivatives exhibited the highest antibacterial activity with MICs (0.892–3.744 μg/mL) lower than that of chloramphenicol (2.019–8.078 μg/mL) against E. coli, P. aeruginosa, and S. marcescens. Prediction of ADME parameters, pharmacokinetics, and substrate promiscuity revealed that these new pyridazines could be promising drug candidates. Cytotoxic studies on rat hepatocytes showed how much safe these new pyridazines on living organisms (IC₅₀>64 μg/mL). MOE docking studies showed a good overlay of these new pyridazines with co‐crystallized ligand within an E. coli DNA gyrase subunit B active sites (4KFG).     

Design,Synthesis, Molecular Docking,and Molecular Dynamics Simulation Studies of Novel 3-Hydroxypyridine-4-one Derivatives as Potential Acetylcholinesterase Inhibitors

Researchers have focused on inhibiting acetylcholinesterase for Alzheimer's disease treatment. In this study, some novel AChE inhibitors were synthesized using hydroxypyridin-4-one plus benzylpiperidine scaffolds which were evaluated using Ellman's method. Accordingly, ((1-(4-methoxyphenethyl)piperidin-4-yl)amino)methyl)-5-hydroxy-1-methylpyridin-4(1H)-one (VII_d) showed weaker but promising AChE inhibition compared to donepezil (IC₅₀=143.090 nM). The average RMSD values of VII_d was found to be 2.25 indicated less structural changes in the active site residues. The phenyl group of the phenyl-ethyl-N-piperidine moiety of VII_d formed hydrophobic interactions with Trp285 and Tyr340. There was a π-cation interaction between nitrogen atom of piperidine ring and Phe294. Another π-cation interaction was found between type 2 amine of linker and Trp85. Piperidine ring interacted with Tyr336, Tyr123, and Phe337 through hydrophobic interactions. Indeed, the VII_d was predicted to be absorbed across the gastrointestinal tract, though it may be pumped out by P-gp. Indeed, VIId can permeate through the blood brain barrier. MD simulation studies revealed that benzyloxy moiety plays a role similar to benzylpiperidine moiety of donepezil in binding to the active site residues. Also, carbonyl group functioned similar to indanone ketone group. Overall; further research on VII_d may lead to introduction of a novel class of AChE inhibitors.     

Synthesis,Characterization and Evaluation of Cytotoxic Activities of Novel Aziridinyl Phosphonic Acid Derivatives

New aziridine 2‐phosphonic acids were prepared by monohydrolysis of the aziridine 2‐phosphonates that were obtained by the modified Gabriel?Cromwell reaction of vinyl phosphonate or α‐tosylvinyl phosphonate with a primary amine or a chiral amine. The cellular cytotoxicity of these compounds was tested against the HCT‐116 colorectal cancer cell lines and the CCD‐18Co normal colon fibroblast lines using the MTT assay. Three of the synthesized phosphonic acid derivatives 2e (ethyl hydrogen {(2S)‐1‐[(1S)‐1‐(naphthalen‐2‐yl)ethyl]aziridin‐2‐yl}phosphonate), 2h (ethyl hydrogen (1‐benzylaziridin‐2‐yl)phosphonate), and 2i (ethyl hydrogen (1‐cyclohexylaziridin‐2‐yl)phosphonate) showed higher cytotoxicity than the reference cancer treatment agent etoposide. Cell death was through a robust induction of apoptosis even more effectively than etoposide, a well‐known apoptosis inducing agent.     

Design,Synthesis, and Insecticidal Activities of Novel N-Pyridylpyrazole Amide Derivatives Containing a Maleimide

To discover ‘me-better’ insecticidal active molecules targeting ryanodine receptors (RyRs), a series of novel N-pyridylpyrazole amide derivatives containing a maleimide were designed and synthesized in accordance with the prior investigations of our group. Preliminary bioassay findings indicated some compounds containing a maleimide exhibited good larvicidal activities against lepidopteran pests at a concentration of 500 mg L⁻¹. Compound 9 j showed 60 % larvicidal activities against M. Separata at 50 mg L⁻¹. Compound 9 b exhibited 40 % larvicidal activities against P. xylostella at 50 mg L⁻¹. Molecular docking study indicated that H-bonds, π–π interaction and cation-π interaction made for the binding of compounds 9 b , 9 j with P. Xylostella RyR. These results indicated that compounds 9 b and 9 j could be developed as novel and promising insecticidal leads.     

Phosphonic and Phosphinic Acid Derivatives as Novel Tyrosinase Inhibitors: Kinetic Studies and Molecular Docking

A dozen of phosphonic and phosphinic acid derivatives containing pyridine moiety were synthesized and its inhibitory activity toward mushroom tyrosinase was investigated. Moreover, molecular docking of these compounds to the active site of the enzyme was performed. All the compounds ( 1 – 10 ) demonstrated the inhibitory effect with the IC₅₀ and inhibition constants ranging millimolar concentrations. The obtained results indicate that the compounds show different types of inhibition (competitive, noncompetitive, mixed), but all of them are reversible inhibitors. The obtained outcomes allowed to make the structure–activity relationship (SAR) analysis. Compound 4 ([(benzylamino)(pyridin‐2‐yl)methyl]phenylphosphinic acid) revealed the lowest IC₅₀ value of 0.3 mm and inhibitory constant of K_i 0.076 mm , with noncompetitive type and reversible mechanism of inhibition. According to SAR analysis, introducing bulky phenyl moieties to phosphonic and amino groups plays an important role in the inhibitory potency on activity of mushroom tyrosinase and could be useful in design and development of a new class of potent organophosphorus inhibitors of tyrosinase. Combined results of molecular docking and SAR analysis can be helpful in designing novel tyrosinase inhibitors of desired properties. They may have broad application in food industry and cosmetology.     

Antiproliferative Noscapinoids Bearing an Amidothiadiazole Scaffold as Apoptosis Inducers: Design,Synthesis and Molecular Docking

Noscapine an FDA-approved antitussive agent. With low cytotoxicity with higher concentrations, noscapine and its derivatives have been shown to have exceptional anticancer properties against a variety of cancer cell lines. In order to increase its potency, in this study, we synthesized a series of new amido-thiadiazol coupled noscapinoids and tested their cytotoxicity in vitro. All of the newly synthesised compounds demonstrated potent cytotoxic potential, with IC₅₀ values ranging from 2.1 to 61.2 μM than the lead molecule, noscapine (IC₅₀ value ranges from 31 to 65.5 μM) across all cell lines, without affecting normal cells (IC₅₀ value is>300 μM). Molecular docking of all these molecules with tubulin (PDB ID: 6Y6D, resolution 2.20 Å) also revealed better binding affinity (docking score range from −5.418 to −9.679 kcal/mol) compared to noscapine (docking score is −5.304 kcal/mol). One of the most promising synthetic derivatives 6aa (IC₅₀ value ranges from 2.5 to 7.3 μM) was found to bind tubulin with the highest binding affinity (ΔG_binding is −28.97 kcal/mol) and induced apoptosis in cancer cells more effectively.     

Antifungal Activity,Structure-Activity Relationship and Molecular Docking Studies of 1,2,4-Triazole Schiff Base Derivatives

Fourteen novel Schiff base compounds ( AS-1 ∼ AS-14 ) containing 5-amino-1H-1,2,4-triazole-3-carboxylic acid and substituted benzaldehyde were successfully synthesized, and their structures were verified by melting point, elemental analysis (EA) and spectroscopic techniques (Fourier Transform Infra-Red (FT-IR) and Nuclear Magnetic Resonance (NMR)). In vitro hyphal measurements were used to investigate the antifungal activities of the synthesised compounds against Wheat gibberellic, Maize rough dwarf and Glomerella cingulate. The preliminary studies indicated that all compounds had good inhibitory effect on Wheat gibberellic and Maize rough dwarf, among which the compounds of AS-1 (7.44 mg/L, 7.27 mg/L), AS-4 (6.80 mg/L, 9.57 mg/L) and AS-14 (5.33 mg/L, 6.53 mg/L) showed better antifungal activity than that of the standard drug fluconazole (7.66 mg/L, 6.72 mg/L); while inhibitory effect against Glomerella cingulate was poor, only AS-14 (5.67 mg/L) was superior to that of fluconazole (6.27 mg/L). The research of structure-activity relationship exhibited that the introduction of halogen elements on the benzene ring and electron withdrawing groups at the 2,4,5 positions on the benzene ring was beneficial to the improvement of the activity against Wheat gibberellic, while the large steric hindrance was not conducive to the improvement of the activity. Additionally, except for AS-1 , AS-3 and AS-10 , the other compounds had one or several ratio systems to achieve synergistic effect after recombination with pyrimethamine, among which AS-7 had significant synergistic effect and was expected to be a combinated agent with application prospects. Finally, the molecular docking results of isocitrate lyase with Wheat gibberellic displayed that the presence of hydrogen bonds enabled stable binding of compounds to receptor proteins, and the residues of ARG A: 252, ASN A: 432, CYS A: 215, SER A: 436 and SER A: 434 were the key residues for their binding. Comparing the docking binding energy and biological activity results, it was revealed that the lower the docking binding energy was, the stronger the inhibitory ability of the Wheat gibberellic, when the same position on the benzene ring was substituted.