Pharmacological study on lignins as a class of anti-HIV agents

一类合成木质素（对香豆酸、阿魏酸和咖啡酸的脱氢聚合物）抑制HIV-1和HIV-2感染的致细胞病变性。聚合物抑制了感染细胞中HIV特异性抗原的表达，也抑制了HIV与细胞的结合，但即使在几乎完全抑制HIV诱导的致细胞病变作用的剂量下也不能完全抑制。这些结果表明，木质素结构，无论是合成的还是天然的，都可以通过一种未知的过程抑制HIV复制，因此证明是一类新的抗HIV药物，可能对治疗AIDS有效。将合成木质素的对香豆酸的脱氢聚合物静脉注射到小鼠体内后，立即、15 min、1 h、5 h收集血清，注射后24 h。将如此获得的血清加入到含有感染了HTLV-IIIB（HIV-1株）的MT-4细胞的测定培养基中。用MTT法测定这些血清制剂对HIV细胞致病性的抑制作用。结果表明，木质素类化合物具有潜在的抗HIV活性，但其作用机制尚未明确;为评价木质素类化合物的遗传毒性，采用鼠伤寒沙门氏菌（Salmonella typhimurium）试验菌株对木质素类化合物进行了致突变性试验，结果表明，木质素类化合物均无致突变性。本文还描述了它们抗诱变性能的初步结果：合成和某些天然木质素对2-硝基芴和1-硝基芘的致突变性有显著的抑制作用，但对AF-2和4-硝基喹啉1-氧化物的致突变性无抑制作用。此外，它们灭活了S9酶，从而抑制了Trp-P1、Trp-P2和Glu-P1的致突变性。

A class of synthetic lignins (dehydrogenation polymers of p-coumaric acid, ferulic acid, and caffeic acid) inhibited cytopathogenicity of HIV-1 and HIV-2 infection. The polymers inhibited expression of HIV-specific antigen in the intected cells and also inhibited HIV-binding to the cells, but not completely, even at doses that almost completely inhibited the HIV-induced cytopathogenic effect. These results suggest that lignin structure, regardless of whether synthetic or natural, may inhibit HIV replication by an unidentified process, and thus prove to be a new class of anti-HIV agents possibly effective in the treatment of AIDS.After the dehydrogenation polymer of p-coumaric acid, a synthetic lignin, was intravenously injected into mice, the serum was collected immediately, 15 min, 1 h, 5 h, and 24 h after the injection. The serum thus obtained was added to the assay medium containing MT-4 cells infected with HTLV-IIIB (an HIV-1 strain). Inhibition of the cytopathogenicity of HIV by these serum preparations was assayd by the MTT method. The result revealed that lignins could be a promising class of anti-HIV agents with an unidentified unique mode of action.For safety assessment on genotoxicity, lignins and related compounds were tested for mutagenicity in Salmonella typhimurium tester strains and none of the compounds examined were proved to be mutagenic. This paper also describes a preliminary result on their antimugtagenic property ; synthetic and some natural lignins suppressed to a remarkable extent mutagenicities of 2-nitrofluorene and 1-nitropyrene, but not those of AF-2 and 4-nitroquinoline 1-oxide. In addition, they inactivated the S9 enzyme resulting in suppression of mutagenicity of Trp-P1, Trp-P2, and Glu-P1.