Design, Synthesis and Various Bioactivity of Acylhydrazone-Containing Matrine Analogues

Compounds with acylhydrazone fragments contain amide and imine groups that can act as electron donors and acceptors, so they are easier to bind to biological targets and thus generally exhibit significant biological activity. In this work, acylhydrazone fragments were introduced to the C-14 or C-11 position of matrine, a natural alkaloid, aiming to enhance their biological activities. The result of this bioassay showed that many synthesized compounds exhibited excellent anti-virus activity against the tobacco mosaic virus (TMV). Seventeen out of 25 14-acylhydrazone matrine derivatives and 17 out of 20 11-butanehydrazone matrine derivatives had a higher inhibitory activity against TMV than the commercial antiviral agent Ribavirin (the in vitro activity, in vivo inactivation, curative and protection activities at 500 mu g/mL were 40.9, 36.5 +/- 0.9, 38.0 +/- 1.6 and 35.1 +/- 2.2%, respectively), and four 11-butanehydrazone matrine derivatives even had similar to or higher activity than the most efficient antiviral agent Ningnanmycin (55.4, 57.8 +/- 1.4, 55.3 +/- 0.5 and 60.3 +/- 1.2% at 500 mu g/mL for the above four test modes). Among them, the N-benzyl-11-butanehydrazone of matrine formed with 4-bromoindole-3-carboxaldehyde exhibited the best anti-TMV activity (65.8, 71.8 +/- 2.8, 66.8 +/- 1.3 and 69.5 +/- 3.1% at 500 mu g/mL; 29, 33.5 +/- 0.7, 24.1 +/- 0.2 and 30.3 +/- 0.6% at 100 mu g/mL for the above four test modes), deserving further investigation as an antiviral agent. Other than these, the two series of acylhydrazone-containing matrine derivatives were evaluated for their insecticidal and fungicidal activities. Several compounds were found to have good insecticidal activities against diamondback moth (Plutella xylostella) and mosquito larvae (Culex pipiens pallens), showing broad biological activities.

Automated summary

Compounds with acylhydrazone fragments, containing amide and imine groups, exhibit significant biological activity due to their ability to act as electron donors and acceptors, making them easier to bind to biological targets. In this study, acylhydrazone fragments were introduced to matrine, a natural alkaloid, in order to enhance its biological activity. The synthesized compounds showed excellent anti-virus activity against the tobacco mosaic virus (TMV) and also demonstrated insecticidal and fungicidal activities against diamondback moth and mosquito larvae.