Lapachol (1) is a well-studied natural product isolated from plants of the Bignoniaceae family and demonstrates diverse biological effects. Historically, chemical transformation of the lapachol scaffold has yielded new derivatives with impressive biological activity and rich chemical diversity. β-lapachone (2), α-lapachone (3), and 2-acetylfuronaphthoquinone (4) are examples of analogs derived from lapachol that show superior antitumor activity compared with the natural product. In the present study, novel indane carboxylic acid: 2,2-dimethyl-2,3-dihydroindeno[1,2-b]pyran-4,5-dione (9) and methyl 5-hydroxy-2,2-dimethyl-2,3,4,5-tetrahydroindeno[1,2-b]pyran-5-carboxylate (10) and naphthoquinone derivatives were synthesized from lapachol with structural similarities to the antitumor lapachol derivatives. The synthesized compounds were evaluated for antiproliferative activities against a panel of human cancer cell lines including in vitro models for neuroblastoma, melanoma, glioblastoma, and non-small cell lung cancer. As expected, the most potent derivatives were those incorporating β-naphthoquinone and α-naphthoquinono[2,3-b]furan skeletons. Many of these compounds possessed nanomolar to single digit micromolar antiproliferative potency. However, the most interesting analog evaluated was the dione 9 with an indeno[1,2-b]pyran skeleton, which demonstrated potent cytotoxic activity. The current investigation identified several new lead compounds that could be used as starting points for anticancer drug discovery.

中文翻译：

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拉帕胆中萘醌和茚满羧酸对人癌细胞系的抗增殖活性

拉帕醇（1）是从植物中分离的充分研究的天然产物紫葳家族并演示了不同的生物学作用。从历史上看，lapachol支架的化学转化产生了具有令人印象深刻的生物活性和丰富的化学多样性的新衍生物。β-拉帕酮（2），α-拉帕酮（3）和2-乙酰基呋喃萘醌（4）是衍生自拉帕酚的类似物的实例，其与天然产物相比显示出优异的抗肿瘤活性。在本研究中，新型茚满羧酸：2,2-二甲基-2,3-二氢茚并[1,2-b]吡喃-4,5-二酮（9）和甲基5-羟基-2,2-二甲基- 2,3,4,5-四氢茚并[1,2-b]吡喃-5-羧酸酯（10）和萘醌衍生物是从拉帕酚合成的，其结构与抗肿瘤拉帕酚衍生物相似。评价合成的化合物对一组人类癌细胞系的抗增殖活性，所述人类癌细胞系包括神经母细胞瘤，黑素瘤，胶质母细胞瘤和非小细胞肺癌的体外模型。不出所料，最有效的衍生物是那些掺有β-萘醌和α-萘醌[2,3-b]呋喃骨架的衍生物。这些化合物中的许多化合物都具有纳摩尔至个位数的微摩尔抗增殖能力。但是，最有趣的类似物是dione 9具有茚并[1,2-b]吡喃骨架，具有强大的细胞毒活性。当前的调查确定了几种新的铅化合物，可以用作抗癌药物发现的起点。