Improving Regulation of Enzymatic and Non-Enzymatic Antioxidants and Stress-Related Gene Stimulation in Cucumber mosaic cucumovirus-Infected Cucumber Plants Treated with Glycine Betaine, Chitosan and Combination.

Cucumber mosaic cucumovirus (CMV) is a deadly plant virus that results in crop-yield losses with serious economic consequences. In recent years, environmentally friendly components have been developed to manage crop diseases as alternatives to chemical pesticides, including the use of natural compounds such as glycine betaine (GB) and chitosan (CHT), either alone or in combination. In the present study, the leaves of the cucumber plants were foliar-sprayed with GB and CHT-either alone or in combination-to evaluate their ability to induce resistance against CMV. The results showed a significant reduction in disease severity and CMV accumulation in plants treated with GB and CHT, either alone or in combination, compared to untreated plants (challenge control). In every treatment, growth indices, leaf chlorophylls content, phytohormones (i.e., indole acetic acid, gibberellic acid, salicylic acid and jasmonic acid), endogenous osmoprotectants (i.e., proline, soluble sugars and glycine betaine), non-enzymatic antioxidants (i.e., ascorbic acid, glutathione and phenols) and enzymatic antioxidants (i.e., superoxide dismutase, peroxidase, polyphenol oxidase, catalase, lipoxygenase, ascorbate peroxidase, glutathione reductase, chitinase and ß-1,3 glucanase) of virus-infected plants were significantly increased. On the other hand, malondialdehyde and abscisic acid contents have been significantly reduced. Based on a gene expression study, all treated plants exhibited increased expression levels of some regulatory defense genes such as PR1 and PAL1. In conclusion, the combination of GB and CHT is the most effective treatment in alleviated virus infection. To our knowledge, this is the first report to demonstrate the induction of systemic resistance against CMV by using GB.

Opuntin B, the antiviral protein isolated from prickly pear (Opuntia ficus-indica (L.) Miller) cladode exhibits ribonuclease activity.

An antiviral protein, designated Opuntin B, was purified from Prickly Pear (Opuntia ficus-indica (L.) Miller) Cladode by heat treatment of the extract, protein precipitation by ammonium sulfate treatment followed by ion-exchange chromatography. Assessment of enzymatic activity of the purified protein showed that it degrades total plant genomic RNA, while causing electrophoretic mobility shifting of Cucumber mosaic virus (CMV) RNAs. However, heat-denatured viral RNA became sensitive to degradation upon treatment with antiviral protein. Opuntin B had no DNase activity on native and heat-denatured apricot genomic DNA, and on PCR-amplified coat protein gene of CMV. Using CMV as prey protein and Opuntin B as bait protein, no interaction was found between the antiviral protein and viral coat protein in far western dot blot analysis.

Synthesis of Anthranilic Diamide Derivatives Containing Moieties of Trifluoromethylpyridine and Hydrazone as Potential Anti-Viral Agents for Plants.

A series of novel anthranilic diamide derivatives (5a-5ab) containing moieties of trifluoromethylpyridine and hydrazone was designed and synthesized. The synthesized compounds were evaluated in vivo for their activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Most of the synthesized compounds displayed good to excellent antiviral activities. The compounds 5i, 5k, 5s, 5w, 5x, and 5z had the curative activity over 65% against TMV at the concentration of 500 µg/mL, which were significantly higher than those of ningnanmycin (55.0%) and ribavirin (37.9%). Notably, the curative activity of compound 5i was up to 79.5%, with the EC50 value of 75.9 µg/mL, whereas the EC50 value of ningnanmycin was 362.4 µg/mL. The pot experiments also further demonstrated the significantly curative effect of 5i. Meanwhile, compounds 5h, 5p and 5x displayed more protective activities on TMV than that of ningnanmycin. Moreover, compounds 5a, 5e, 5f, and 5i showed inactivation activity similar to ningnanmycin at 500 µg/mL, and the EC50 value of 5e (41.5 µg/mL) was lower than ningnanmycin (50.0 µg/mL). The findings of transmission electron microscopic (TEM) indicated that the synthesized compounds exhibited strong and significant binding affinity to TMV coat protein (CP) and could obstruct the self-assembly and increment of TMV particles. Microscale thermophoresis (MST) studies on TMV-CP and CMV CP revealed that some of the active compounds, particularly 5i, exhibited a strong binding capability to TMV-CP or CMV-CP. This study revealed that anthranilic diamide derivatives containing moieties of trifluoromethylpyridine and hydrazone could be used as novel antiviral agents for controlling the plant viruses.

Design, Synthesis, and Bioactivity Evaluation of Novel Isoxazole-Amide Derivatives Containing an Acylhydrazone Moiety as New Active Antiviral Agents.

As a continuation of our efforts to discover and develop "me-better" active molecules, in this study, a series of novel isoxazole-amide derivatives containing an acylhydrazone moiety were synthesized and evaluated for their antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). Antiviral bioassays indicated that some of the target compounds exhibited better in vivo antiviral activities against TMV and CMV than those of Ningnanmycin (NNM). Especially, the compound 7t exhibited the best curative, protection, and inactivation activities against TMV and CMV which were superior to those of NNM. Meanwhile, our present work also revealed that compound 7t could enhance the defense-related enzyme activity and increase the chlorophyll content in tobacco leaves to induce resistance and enhance plant tolerance to TMV infection.

A new strategy to control Cucumber mosaic virus using fabricated NiO-nanostructures.

This study was carried out to fabricate nickel oxide nanostructures (NONS) and to evaluate its ability to control Cucumber mosaic virus (CMV) by direct antiviral activity as well as induction of systemic resistance in treated cucumber plants. The efficacy of nickel oxide nanostructures for control CMV in cucumber plants was biologically evaluated by a reduction in disease severity, reduction in CMV accumulation and expression of regulatory and defense-related genes. Cucumber plants treated with nickel oxide nanostructures showed incredible suppression of CMV infection compared with non-treated plants. The enzyme-linked immunosorbent assay (ELISA) showed a marked reduction in CMV accumulation in cucumber plants treated with nickel oxide nanostructures compared to untreated plants. Based on real-time polymerase chain reaction (RT-PCR) test, cucumber plants treated with nickel oxide nanostructures showed increased expression of regulatory and defense-related genes concerned in salicylic acid (SA) and jasmonic acid (JA)/ethylene (ET) signaling pathways. NONS nanostructures showed direct antiviral activity against CMV resulted in significant reduction in CMV severity and titer relative to untreated plants. Treatment with nickel oxide nanostructures significantly improved cucumber fresh and dry weights as well as number of leaves. The induction of systemic resistance towards CMV by NONS nanostructures considered a novel strategy and first report.

Synthesis, Antiviral Activity, and Mechanisms of Purine Nucleoside Derivatives Containing a Sulfonamide Moiety.

Novel purine nucleoside derivatives containing a sulfonamide moiety were prepared, as well as their antiviral activities against potato virus Y (PVY), cucumber mosaic virus (CMV), and tobacco mosaic virus (TMV) were evaluated. The antiviral mechanisms of the compounds were investigated. Results showed that most of the compounds had good antiviral activities. Compound 5 at 500 µg/mL exhibited excellent curative and protective activities of 52.5% and 60.0% and of 52.0% and 60.2% for PVY and CMV, respectively, which are higher than those of ningnanmycin (48.1%, 49.6%; 45.3%, 47.7%), ribavirin (38.3%, 48.2%; 40.8%, 45.5%), and chitosan oligosaccharide (32.5%, 33.8%; 35.1%, 34.6%). Moreover, compound 5 displayed good inactivating activity against TMV, with an EC50 value of 48.8 µg/mL, which is better than that of ningnanmycin (84.7 µg/mL), ribavirin (150.4 µg/mL), and chitosan oligosaccharide (521.3 µg/mL). The excellent antiviral activity of compound 5 is related to its immune induction effect which can regulate the physiological and biochemical processes in plants, including defense-related enzyme activities, defense-related genes, and photosynthesis-related proteins. These results indicate that purine nucleoside derivatives containing a sulfonamide moiety are worthy of further research and development as new antiviral agents.

Inhibition of Satellite RNA Associated Cucumber Mosaic Virus Infection by Essential Oil of Micromeria croatica (Pers.) Schott.

The present results dealing with the antiphytoviral activity of essential oil indicate that these plant metabolites can trigger a response to viral infection. The essential oil from Micromeria croatica and the main oil components ß-caryophyllene and caryophyllene oxide were tested for antiphytoviral activity on plants infected with satellite RNA associated cucumber mosaic virus. Simultaneous inoculation of virus with essential oil or with the dominant components of oil, and the treatment of plants prior to virus inoculation, resulted in a reduction of virus infection in the local and systemic host plants. Treatment with essential oil changed the level of alternative oxidase gene expression in infected Arabidopsis plants indicating a connection between the essential oil treatment, aox gene expression and the development of viral infection.

Antiviral activity of aconite alkaloids from Aconitum carmichaelii Debx.

Four diterpenoid alkaloids, namely, (a) hypaconitine, (b) songorine, (c) mesaconitine and (d) aconitine, were isolated from the ethanol root extract of Aconitum carmichaelii Debx. The antiviral activities of these alkaloids against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) were evaluated. Antiviral activity test in vivo showed that compounds a and c, which were C19-diterpenoid alkaloids, showed inactivation efficacy values of 82.4 and 85.6% against TMV at 500 µg/mL, respectively. By contrast, compound c presented inactivation activity of 52.1% against CMV at 500 µg/mL, which was almost equal to that of the commercial Ningnanmycin (87.1% inactivation activity against TMV and 53.8% inactivation activity against CMV). C19-Diterpenoid alkaloids displayed moderate to high antiviral activity against TMV and CMV at 500 µg/mL, dosage plays an important role in antiviral activities. This paper is the first report on the evolution of aconite diterpenoid alkaloids for antiviral activity against CMV.

Characterization of a thermostable κ-carrageenase from a hot spring bacterium and plant protection activity of the oligosaccharide enzymolysis product.

BACKGROUND: Seaweed oligosaccharides are environmentally-friendly natural products and their use for disease control in sustainable agriculture is extremely promising. Enzymatic digestion to prepare seaweed oligosaccharides has drawn considerable interest. However, the study of enzymatically degraded products of carrageenan is still in its infancy compared with that of other hydrocolloids such as agar and alginate. To prepare degraded carrageenan on a commercial scale, it is necessary to select superior producer bacterial strains to improve the yield and thermostability of carrageenases. RESULTS: The carrageenan-degrading bacterium Bacillus sp. HT19 was isolated from sediment of a hot spring in Indonesia, and a κ-carrageenase with high activity was purified from the culture supernatant. The purified enzyme, named Car19, had maximum activity (538 U mg-1 ) at 60 °C and pH 7.0. Notably, the enzyme retained >90% of its initial activity after incubation at 60 °C for 24 h. The Ca2+ obviously improved the thermostability of Car19 at 70 °C. The Km and Vmax values of purified Car19 were 0.061 mg mL-1 and 115.13 U mg-1 , respectively, with κ-carrageenan as substrate. Thin-layer chromatography and electrospray ionization mass-spectrometry analysis of hydrolysates indicated that the enzyme exolytically depolymerized κ-carrageenan to neo-carrabiose. The hydrolysate enhanced the resistance of cucumber to cucumber mosaic virus and increased the activity of antioxidant enzymes in infected plants. CONCLUSION: To our knowledge, Car19 is the most thermostable κ-carrageenase reported so far. Its high optimal reaction temperature and thermostability, and unitary hydrolysate constituent, makes Car19 a promising candidate for the preparation of carrageenan oligosaccharides with plant protection activity. © 2018 Society of Chemical Industry.

Syntheses, antiviral activities and induced resistance mechanisms of novel quinazoline derivatives containing a dithioacetal moiety.

A series of novel quinazoline derivatives containing a dithioacetal moiety were designed and synthesized, and their structures were characterized by 1H nuclear magnetic resonance, 13C nuclear magnetic resonance, and high-resolution mass spectrometry. Bioassay results indicated that compound 4b exhibited remarkable protective activity against cucumber mosaic virus (CMV, EC50 = 248.6 µg/mL) and curative activity against potato virus Y (EC50 = 350.5 µg/mL), which were better than those of ningnanmycin (357.7 µg/mL and 493.7 µg/mL, respectively). Moreover, compound 4b could increase the chlorophyll content in plants, improve photosynthesis, and effectively induce tobacco anti-CMV activity.

Antiviral properties and interaction of novel chalcone derivatives containing a purine and benzenesulfonamide moiety.

A new concise and facile method was explored to synthesize a series of novel chalcone derivatives containing a purine and benzenesulfonamide moiety and their antiviral properties were evaluated against TMV and CMV. Biological assays indicated that several of the derivatives exhibited significant anti-TMV and anti-CMV activities in vivo. In particular, compound d2 displayed excellent inactivating activity against TMV, with the EC50 value of 51.65 µg/mL, which was better than that of ribavirin (150.45 µg/mL). Molecular docking showed that there are four hydrogen bonds between compound d2 and TMV coat protein (TMV-CP). Compound d2 demonstrated strong binding capacity to TMV-CP with Ka = 1.58 × 105 L/mol and Kd = 12.16 µM. These findings indicated that chalcone derivatives are worthy of further research and development as templates for new antiviral agents.

Design, Synthesis, Antiviral Bioactivity, and Defense Mechanisms of Novel Dithioacetal Derivatives Bearing a Strobilurin Moiety.

A series of dithioacetal derivatives bearing a strobilurin moiety were designed and synthesized on the basis of our previous work. The antiviral activities of these compounds against Potato virus Y (PVY), Cucumber mosaic virus (CMV), and Tobacco mosaic virus (TMV) were systematically evaluated. Bioassay results indicated that C14 elicited excellent curative and protective activities against PVY, CMV, and TMV. The former had 50% effective concentrations (EC50) of 125.3, 108.9, and 181.7 µg/mL, respectively, and the latter had 148.4, 113.2, and 214.6 µg/mL, respectively, which were significantly superior to those of lead compound 6f (297.6, 259.6, and 582.4 µg/mL and 281.5, 244.3, and 546.3 µg/mL, respectively), Ningnanmycin (440.5, 549.1, and 373.8 µg/mL and 425.3, 513.3, and 242.7 µg/mL, respectively), Chitosan oligosaccharide (553.4, 582.8, and 513.8 µg/mL and 547.3, 570.6, and 507.9 µg/mL, respectively), and Ribavirin (677.4, 690.3, and 686.5 µg/mL and 652.7, 665.4, and 653.4 µg/mL, respectively). Moreover, defensive enzyme activities and RT-qPCR analysis demonstrated that the antiviral activity was associated with the changes of SOD, CAT, and POD activities in tobacco, which was proved by the related proteins of abscisic acid signaling pathway. This work provided a basis for further design, structural modification, and development of dithioacetal derivatives as new antiviral agents.

Novel α,ß-unsaturated amide derivatives bearing α-amino phosphonate moiety as potential antiviral agents.

Based on flexible construction and broad bioactivity of ferulic acid, a series of novel α,ß-unsaturated amide derivatives bearing α-aminophosphonate moiety were designed, synthesized and systematically evaluated for their antiviral activity. Bioassay results indicated that some compounds exhibited good antiviral activities against cucumber mosaic virus (CMV) and tobacco mosaic virus (TMV) in vivo. Especially, compound g18 showed excellent curative and protective activities against CMV, with half-maximal effective concentration (EC50) values of 284.67µg/mL and 216.30µg/mL, which were obviously superior to that of Ningnanmycin (352.08µg/mL and 262.53µg/mL). Preliminary structure-activity relationships (SARs) analysis revealed that the introduction of electron-withdrawing group at the 2-position or 4-position of the aromatic ring is favorable for antiviral activity. Present work provides a promising template for development of potential inhibitor of plant virus.

Facile Synthesis of Novel Vanillin Derivatives Incorporating a Bis(2-hydroxyethyl)dithhioacetal Moiety as Antiviral Agents.

A series of vanillin derivatives incorporating a bis(2-hydroxyethyl)dithioacetal moiety was designed and synthesized via a facile method. A plausible reaction pathway was proposed and verified by computational studies. Bioassay results demonstrated that target compounds possessed good to excellent activities against potato virus Y (PVY) and cucumber mosaic virus (CMV), of which, compound 6f incorporating a bis(2-hydroxyethyl)dithioacetal moiety, exhibited the best curative and protection activities against PVY and CMV in vivo, with 50% effective concentration values of 217.6, 205.7 µg/mL and 206.3, 186.2 µg/mL, respectively, better than those of ribavirin (848.0, 808.1 µg/mL and 858.2, 766.5 µg/mL, respectively), dufulin (462.6, 454.8 µg/mL and 471.2, 465.4 µg/mL, respectively), and ningnanmycin (440.5, 425.3 µg/mL and 426.1, 405.3 µg/mL, respectively). Current studies provide support for the application of vanillin derivatives incorporating bis(2-hydroxyethyl)dithioacetal as new antiviral agents.

Synthesis and Antiviral Activity of Novel 1,4-Pentadien-3-one Derivatives Containing a 1,3,4-Thiadiazole Moiety.

1,4-Pentadien-3-one derivatives derived from curcumin possess excellent inhibitory activity against plant viruses. On the basis of this finding, a series of novel 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety were designed and synthesized, and their structures confirmed by IR, ¹H-NMR, and 13C-NMR spectroscopy and elemental analysis. The antiviral activities of the title compounds were evaluated against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. The assay results showed that most of compounds had remarkable antiviral activities against TMV and CMV, among which compounds 4b, 4h, 4i, 4k, 4o, and 4q exhibited good curative, protection, and inactivation activity against TMV. Compounds 4h, 4i, 4k, 4l, 4o, and 4q exhibited excellent protection activity against TMV, with EC50 values of 105.01, 254.77, 135.38, 297.40, 248.18, and 129.87 µg/mL, respectively, which were superior to that of ribavirin (457.25 µg/mL). In addition, preliminary SARs indicated that small electron-withdrawing groups on the aromatic ring were favorable for anti-TMV activity. This finding suggests that 1,4-pentadien-3-one derivatives containing a 1,3,4-thiadiazole moiety may be considered as potential lead structures for discovering new antiviral agents.

Design, synthesis, antiviral bioactivity and three-dimensional quantitative structure-activity relationship study of novel ferulic acid ester derivatives containing quinazoline moiety.

BACKGROUND: Ferulic acid and quinazoline derivatives possess good antiviral activities. In order to develop novel compounds with high antiviral activities, a series of ferulic acid ester derivatives containing quinazoline were synthesized and evaluated for their antiviral activities. RESULTS: Bioassays indicated that some of the compounds exhibited good antiviral activities in vivo against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV). One of the compounds demonstrated significant curative and protective activities against TMV and CMV, with EC50 values of 162.14, 114.61 and 255.49, 138.81 mg L-1 , respectively, better than those of ningnanmycin (324.51, 168.84 and 373.88, 272.70 mg L-1 ). The values of q2 and r2 for comparative molecular field analysis and comparative molecular similarity index analysis in the TMV (0.508, 0.663 and 0.992, 0.930) and CMV (0.530, 0.626 and 0.997, 0.981) models presented good predictive abilities. CONCLUSION: Some of the title compounds demonstrated good antiviral activities. Three-dimensional quantitative structure-activity relationship models revealed that the antiviral activities depend on steric and electrostatic properties. These results could provide significant structural insights for the design of highly active ferulic acid derivatives. © 2017 Society of Chemical Industry.

Asymmetric Synthesis and Bioselective Activities of α-Amino-phosphonates Based on the Dufulin Motif.

The asymmetric synthesis of enantiomerically pure α-aminophosphonates with high and bioselective activities is a challenge. Here, we report that both enantiomers of α-aminophosphonates bearing the N-benzothiazole moiety can be prepared in high yields (up to 99%) and excellent enantioselectivities (up to 99% ee) by using chiral thiourea organocatalysts. Evaluation of the antiviral activities of our reaction products against cucumber mosaic virus (CMV) led to promising hits with high and selective biological activities, wherein (R)-enantiomers exhibit higher biological activities than the corresponding (S)-enantiomers. Especially, compound (R)-3b with excellent anti-CMV activity (curative activity, 72.3%; protection activity, 56.9%; and inactivation activity, 96.9%) at 500 µg/mL emerged as a potential inhibitor of the plant virus. The difference in the selective bioactivity could be affected by the combination mode of the three-dimensional space between the enantiomers of α-aminophosphonate and cucumber mosaic virus coat protein (CMV-CP) via florescence spectroscopy and molecular docking.

Elevated CO2 impacts bell pepper growth with consequences to Myzus persicae life history, feeding behaviour and virus transmission ability.

Increasing atmospheric carbon dioxide (CO2) impacts plant growth and metabolism. Indirectly, the performance and feeding of insects is affected by plant nutritional quality and resistance traits. Life history and feeding behaviour of Myzus persicae were studied on pepper plants under ambient (aCO2, 400 ppm) or elevated CO2 (eCO2, 650 ppm), as well as the direct impact on plant growth and leaf chemistry. Plant parameters were significantly altered by eCO2 with a negative impact on aphid's life history. Their pre-reproductive period was 11% longer and fecundity decreased by 37%. Peppers fixed significantly less nitrogen, which explains the poor aphid performance. Plants were taller and had higher biomass and canopy temperature. There was decreased aphid salivation into sieve elements, but no differences in phloem ingestion, indicating that the diminished fitness could be due to poorer tissue quality and unfavourable C:N balance, and that eCO2 was not a factor impeding feeding. Aphid ability to transmit Cucumber mosaic virus (CMV) was studied by exposing source and receptor plants to ambient (427 ppm) or elevated (612 ppm) CO2 before or after virus inoculation. A two-fold decrease on transmission was observed when receptor plants were exposed to eCO2 before aphid inoculation when compared to aCO2.

Synthesis, antiviral activity, 3D-QSAR, and interaction mechanisms study of novel malonate derivatives containing quinazolin-4(3H)-one moiety.

A series of novel malonate derivatives containing quinazolin-4(3H)-one moiety were synthesized and evaluated for their antiviral activities against cucumber mosaic virus (CMV). Results indicated that the title compounds exhibited good antiviral activities. Notably, compounds g15, g16, g17, and g18 exhibited excellent curative activities in vivo against CMV, with 50% effective concentration (EC50) values of 208.36, 153.78, 181.47, and 164.72µg/mL, respectively, which were better than that of Ningnanmycin (256.35µg/mL) and Ribavirin (523.34µg/mL). Moreover, statistically valid three-dimensional quantitative structure-activity relationship (3D-QSAR) models with good correlation and predictive power were obtained with comparative molecular field analysis (CoMFA) steric and electrostatic fields (r(2)=0.990, q(2)=0.577) and comparative molecular similarity indices analysis (CoMSIA) with combined steric, electrostatic, hydrophobic and hydrogen bond acceptor fields (r(2)=0.977, q(2)=0.516), respectively. Based on those models, compound g25 was designed, synthesized, and showed better curative activity (146.30µg/mL) than that of compound g16. The interaction of between cucumber mosaic virus coat protein (CMV CP) and g25 with 1:1.83 ratio is typically spontaneous and exothermic with micromole binding affinity by isothermal titration calorimetry (ITC) and fluorescence spectroscopy investigation.

Synthesis, anti-tobacco mosaic virus and cucumber mosaic virus activity, and 3D-QSAR study of novel 1,4-pentadien-3-one derivatives containing 4-thioquinazoline moiety.

A series of novel 1,4-pentadien-3-one derivatives containing 4-thioquinazoline moiety were designed and synthesized. Antiviral bioassay results indicated that most of the title compounds exhibited excellent antiviral activities against tobacco mosaic virus (TMV) and cucumber mosaic virus (CMV) in vivo. Among the title compounds, 7j exhibited the best curative activity against TMV, with a half-maximal effective concentration (EC50) value of 213.5 µg/mL, which was better than that of ningnanmycin (270.9 µg/mL). Meanwhile, 7a showed remarkable protection activity against TMV and curative activity against CMV, with EC50 values of 124.3 and 365.5 µg/mL, respectively, which were superior to those of ningnanmycin (195.1 and 404.9 µg/mL, respectively). Comparative molecular field analysis (CoMFA) and comparative molecular similarity index analysis (CoMSIA) models were generated on the basis of the curative activities against TMV and exhibited good predictive abilities with cross-validated q(2) and non-cross-validated r(2) values for CoMFA and CoMSIA of 0.548, 0.647 and 0.994, 0.993, respectively. These results provided a practical tool for guiding the design and synthesis of novel and more potent 1,4-pentadien-3-one derivatives containing 4-thioquinazoline moiety.