title: Cinnamaldehyde Derivatives Inhibit Coxsackievirus B3-Induced Viral Myocarditis.
abstract: The chemical property of cinnamaldehyde is unstable in vivo, although early experiments have shown its obvious therapeutic effects on viral myocarditis (VMC). To overcome this problem, we used cinnamaldehyde as a leading compound to synthesize derivatives. Five derivatives of cinnamaldehyde were synthesized: 4-methylcinnamaldehyde (1), 4-chlorocinnamaldehyde (2), 4-methoxycinnamaldehyde (3), α-bromo-4-methylcinnamaldehyde (4), and α-bromo-4-chlorocinnamaldehyde (5). Neonatal rat cardiomyocytes and HeLa cells infected by coxsackievirus B3 (CVB3) were used to evaluate their antiviral and cytotoxic effects. In vivo BALB/c mice were infected with CVB3 for establishing VMC models. Among the derivatives, compound 4 and 5 inhibited the CVB3 in HeLa cells with the half-maximal inhibitory concentrations values of 11.38 ± 2.22 μM and 2.12 ± 0.37 μM, respectively. The 50% toxic concentrations of compound 4 and 5-treated cells were 39-fold and 87-fold higher than in the cinnamaldehyde group. Compound 4 and 5 effectively reduced the viral titers and cardiac pathological changes in a dose-dependent manner. In addition, compound 4 and 5 significantly inhibited the secretion, mRNA and protein expressions of inflammatory cytokines TNF-α, IL-1β and IL-6 in CVB3-infected cardiomyocytes, indicating that brominated cinnamaldehyde not only improved the anti-vital activities for VMC, but also had potent anti-inflammatory effects in cardiomyocytes induced by CVB3.
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Qiang
authors.initials: XQ
authors.lastname: Li
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xiao-Xiao
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Pharmacology, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xue-Ying
authors.initials: XY
authors.lastname: Wang
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Xie
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Xin-Xin
authors.initials: XX
authors.lastname: Liu
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Ding
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.affiliation: Department of Natural Medicine and Institute of Materia Medica, School of Pharmacy, Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Si-Wang
authors.initials: SW
authors.lastname: Wang
keywords: Anti-inflammatory; Cinnamaldehyde; Coxsackievirus B3; Myocarditis