Matrix metalloproteinases (MMPs) are zinc-dependent extracellular matrix remodeling endopeptidases. MMPs cleave various matrix proteins such as collagen, elastin, gelatin and casein. MMPs are often implicated in pathological processes, such as cancer progression including metastasis. Meanwhile, microorganisms produce various secondary metabolites having unique structures. We designed and synthesized dehydroxymethylepoxyquinomicin (DHMEQ) based on the structure of epoxyquinomicin C derived from Amycolatopsis as an inhibitor of NF-κB. This compound inhibited cancer cell migration and invasion. Since DHMEQ is comparatively unstable in the body, we designed and synthesized a stable DHMEQ analog, SEMBL. SEMBL also inhibited cancer cell migration and invasion. We also looked for inhibitors of cancer cell migration and invasion from microbial culture filtrates. As a result, we isolated a known compound, ketomycin, from Actinomycetes. DHMEQ, SEMBL, and ketomycin are all NF-κB inhibitors, and inhibited the expression of MMPs in the inhibition of cellular migration and invasion. These are all compounds with comparatively low toxicity, and may be useful for the development of anti-metastasis agents.

基质金属蛋白酶（MMP）是锌依赖性细胞外基质重塑内肽酶。MMP裂解各种基质蛋白，例如胶原蛋白，弹性蛋白，明胶和酪蛋白。MMP通常与病理过程有关，例如癌症进展（包括转移）。同时，微生物产生具有独特结构的各种次级代谢产物。我们基于epoxyquinomicin的C衍生自结构设计和dehydroxymethylepoxyquinomicin（DHMEQ）合成拟无枝酸作为NF-κB的抑制剂。该化合物抑制癌细胞的迁移和侵袭。由于DHMEQ在体内相对不稳定，因此我们设计并合成了稳定的DHMEQ类似物SEMBL。SEMBL还抑制癌细胞的迁移和侵袭。我们还从微生物培养滤液中寻找癌细胞迁移和侵袭的抑制剂。结果，我们从放线菌中分离出一种已知的化合物酮霉素。DHMEQ，SEMBL和酮霉素均为NF-κB抑制剂，在抑制细胞迁移和侵袭中抑制MMPs的表达。这些都是毒性较低的化合物，可用于开发抗转移剂。