ABSTRACT
This work reports the synthesis of quinolone-N-acylhydrazone hybrids, namely 6-R-N'-(2-hydxoxybenzylidene)-4-oxo-1,4-dihydroquinoline-3-carbohydrazide (R = H: 5a, F: 5b, Cl: 5c and Br: 5d), which exhibited excellent activity against arbovirus Zika (ZIKV) and Chikungunya (CHIKV). In vitro screening towards ZIKV and CHIKV inhibition revealed that all substances have significant antiviral activity, most of them being more potent than standard Ribavirin (5a-d: EC50 = 0.75-0.81 µM, Ribavirin: EC50 = 3.95 µM for ZIKV and 5a-d: 1.16-2.85 µM, Ribavirin: EC50 = 2.42 µM for CHIKV). The quinolone-N-acylhydrazone hybrids were non-toxic against Vero cells, in which compounds 5c and 5d showed the best selectivities (SI = 1410 and 630 against ZIKV and CHIKV, respectively). Antiviral activity was identified by inhibition of viral RNA production in a dose-dependent manner. In the evaluation of the time of addition of the compounds, we observed that 5b and 5c remain with strong effect even in the addition for 12 h after infection. The above results indicate that quinolone-N-acylhydrazones represent a new and promising class to be further investigated as anti-ZIKV and anti-CHIKV agents.
Subject(s)
Chikungunya virus/drug effects , Quinolones/therapeutic use , Zika Virus/drug effects , Animals , Chlorocebus aethiops , Humans , Quinolones/pharmacologyABSTRACT
This study examined in rats the subchronic toxicity and anti- HSV-1activity after oral administration of dolabelladienetriol (D1), a diterpene isolated from the seaweed Dictyota pfaffii. In subchronic toxicity (SCT) tests, female rats received D1 by gavage 15 mg/kg/day (n = 5) for 50 days, and general behavior, death, hematological, biochemical and histological changes in the liver, kidney, stomach, and duodenum were determined. For the anti-HSV-1 activity, female mice were infected and treated orally with a dose of 20 mg/kg (n = 5) twice a day with D1 and any lesions in the skin were then recorded for 18 days. Dolabelladienetriol in SCT did not significantly change behavior, body weight, hematological or biochemical profiles. The liver and kidneys, however, showed some alterations in rats treated with D1, similar to those in rats treated with ACV, while the other tissues had no significant changes. The anti-HSV-1 activity of D1 had a similar efficacy to the ACV drug control in mice. Our results showed that D1 has potential commercial development as a new HSV-1drug.
Subject(s)
Antiviral Agents/toxicity , Herpesvirus 1, Human/drug effects , Seaweed/chemistry , Animals , Animals, Laboratory , Female , Mice , Rats , Rats, Wistar , Toxicity Tests, SubchronicABSTRACT
BACKGROUND: Matrix metalloproteinases and their inhibitors might be involved in enamel formation. AIM: This study aimed to evaluate the association between polymorphisms in MMP2, MMP3, MMP9, MMP20, TIMP1, and TIMP2 with white spot lesions (WSL) and early childhood caries (ECC). DESIGN: A cross-sectional study was performed on 786 children aged from 2 to 6 years in Brazil. After clinical evaluation, they were classified into groups with disease (the presence of WSL and/or ECC) and without disease (the absence of WSL or ECC). Genotyping of the selected polymorphisms was carried out with TaqMan real-time PCR, using genomic DNA extracted from buccal cells. Allele and genotype frequencies were compared between groups. Chi-square test, odds ratio (OR), and logistic regression were used (P ≤ 0.05). RESULTS: The dmft score was 1.3 (SD: 2.4), and 41.34% of the children have at least one caries lesion. In MMP9, the GG genotype was more frequent in the group without disease (P = 0.006). In a recessive model, WSL was associated with the marker rs1711437 in MMP20 (P = 0.019; OR = 1.20, 95% CI 1.02-1.42). The marker rs1784418 in MMP20 showed an association between the allele G distribution for the WSL group (P = 0.020; OR = 0.73, 95% CI 0.55-0.96). CONCLUSION: MMP9 and MMP20 are involved in WSL and ECC development.
Subject(s)
Dental Caries/genetics , Matrix Metalloproteinases/genetics , Tissue Inhibitor of Metalloproteinase-1/genetics , Tissue Inhibitor of Metalloproteinase-2/genetics , Alleles , Child , Child, Preschool , Cross-Sectional Studies , DNA/genetics , Dental Caries/enzymology , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Humans , Isoenzymes , Male , Mouth Mucosa , Polymorphism, Genetic , Real-Time Polymerase Chain Reaction , Risk FactorsABSTRACT
Bovine herpesvirus type 5 (BoHV-5) is an etiologic agent of meningoencephalitis in cattle. The aim of this study was to evaluate the antiviral potential of a series of synthetic Mannich bases derived from lawsone and to investigate at which stage of the BoHV-5 replicative cycle the compounds might be acting. The most potent and selective inhibitor exhibited CC50 and EC50 values of 1867 µM ± 8.3 and 3.8 µM ± 1.2, respectively (ACV: 989 µM ± 2 and 166 µM ± 2, respectively).
