Synthesis, characterization and antinociceptive properties of the lappaconitine salts

Abstract

A series of diterpene alkaloid derivatives (1-6) are prepared by reaction of the lappaconitine (0) with the corresponding organic or inorganic acid. The lappaconitine was isolated from the root of Aconitum sinomontanum Nakai in Gansu Province in China. The structures of all newly synthesized compounds were established by analytical and spectral data. In particular, the configurations of compounds 0-3 were determined by X-ray single-crystal diffraction. The analgesic potential has been investigated. Among the compounds tested, all derivatives (1-6) produced antinociceptive effects in a mouse model of acute pain, without inducing undesirable side effects. Furthermore, lappaconitine sulphate exhibited a pronounced analgesic activity. Thus, the present findings have demonstrated that lappaconitine sulphate is a promising analgesic agent and could emerge as a promising analgesic agent for further research work.

Lappaconitine Sulfate Inhibits Proliferation and Induces Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells through the Reactive Oxygen Species-Dependent Mitochondrial Pathway

“…Regents LA (pure > 97.7%) were purchased from Gansu Xinlan Pharmaceutical Co., Ltd. LS (pure > 98.2% ) was synthesized according to the methods of Sun et al [11].…”

“…Furthermore, the combination of LA and the chemotherapeutic agent oxaliplatin could enhance oxaliplatin-induced apoptosis in A549 cells [10]. Compared with LA and LH, LA sulfate (LS) exhibited a greater solubility in water and pronounced analgesic activity, without inducing undesirable side effects [11]. More importantly, we have previously reported that LS exhibited distinct antitumor effects via antiproliferation and the induction of apoptosis [12,13].…”

C18-diterpenoid alkaloids in tribe Delphineae (Ranunculaceae): phytochemistry, chemotaxonomy, and bioactivities

“… 96 In addition, the analgesic activity of LA salts is also affected by the kinds of ions, for example it was reported that the analgesic effect of LA hydrochloride is worse than that of its hydrobromide, 97 while another study revealed that LA sulfate exhibited a more pronounced analgesic activity than other salt forms. 98 …”

Classification, Toxicity and Bioactivity of Natural Diterpenoid Alkaloids

“…Almost all of the C 20 -diterpenoid alkaloids contain oxygenated groups. However, in contrast to the C 19 -diterpenoid alkaloids, C 20 -DAs possess the following distinctive features [ 113 , 114 , 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 , 131 , 132 , 133 , 134 , 135 , 136 , 137 , 138 , 139 , 140 , 141 , 142 , 143 , 144 , 145 , 146 , 147 , 148 , 149 , 150 , 151 , 152 , 153 , 154 , 155 , 156 , 157 ]: Most of them do not contain a methoxy group in their structures as C 19 -DAs [ 108 ]; Some alkaloids contain an acetoxy group or benzoyloxy ester group, or both, and do not incl...…”

“…Lappaconitine (C18-DAs) shows pain-relief properties. However, lappaconitine sulfate, obtained by the modification of lappaconitine, exerts a more noticeable analgesic action than lappaconitine, which is poorly soluble in water [ 139 , 140 ].…”