Synthesis and in vitro evaluation of imidazole-based wakayin analogues

Hoang, Hung; Huang, Xiaofen; Skibo, Edward B.

doi:10.1039/b806883f

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…Imidazole analogs of wakayin are cytotoxic (selectively against cells with the vascular endothelial growth factor receptor) but were not assayed for Top1 inhibition. 229 In 2009, another quinone alkaloid class was reported-the calothrixins, isolated from Cyanobacter calothrix. 230 These natural products were tested against Top1 because of their structural similarity to other Top1 poisons.…”

Section: Non-cpt Natural Productsmentioning

confidence: 99%

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Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Cinelli

2018

Medicinal Research Reviews

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Topoisomerases are DNA processing enzymes that relieve supercoiling (torsional strain) in DNA, are necessary for normal cellular division, and act by nicking (and then religating) DNA strands. Type 1B topoisomerase (Top1) is overexpressed in certain tumors, and the enzyme has been extensively investigated as a target for cancer chemotherapy. Various chemical agents can act as “poisons” of the enzyme’s religation step, leading to Top1‐DNA lesions, DNA breakage, and eventual cellular death. In this review, agents that poison Top1 (and have thus been investigated for their anticancer properties) are surveyed, including natural products (such as camptothecins and indolocarbazoles), semisynthetic camptothecin and luotonin derivatives, and synthetic compounds (such as benzonaphthyridines, aromathecins, and indenoisoquinolines), as well as targeted therapies and conjugates. Top1 has also been investigated as a therapeutic target in certain viral and parasitic infections, as well as autoimmune, inflammatory, and neurological disorders, and a summary of literature describing alternative indications is also provided. This review should provide both a reference for the medicinal chemist and potentially offer clues to aid in the development of new Top1 poisons.

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Section: Non-cpt Natural Productsmentioning

confidence: 99%

“…Aza‐analogs of 37 were prepared, some of which displayed anti‐Top1 activity. Imidazole analogs of wakayin are cytotoxic (selectively against cells with the vascular endothelial growth factor receptor) but were not assayed for Top1 inhibition …”

Section: Topoisomerase Poisonsmentioning

confidence: 99%

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Cinelli

2018

Medicinal Research Reviews

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“…The first part of the synthesis is the preparation of the key intermediate 30 from which various substituted analogues were made. The synthesis started with the nitration of m -chlorophenol followed by methylation of the phenolic OH to yield 3-chloro-4-nitroanisole 27 [52]. Treatment of compound 27 with ethanolamine resulted in nucleophilic aromatic substitution to afford compound 28 .…”

Section: Synthetic Studiesmentioning

confidence: 99%

“…The four analogues of wakayin based on diimidazo[1,5,4-de, 1,5,4-h]-quinoxaline ( 35a-d ) that were described in Scheme 5 were subjected to an extensive investigation for their cytostatic and cytotoxic activity using a 60 human cancer cell-line panel consisting of the major histological tissue types [52]. The concentrations of drug required for 50% growth inhibition (GI 50 ) , total growth inhibition (TGI), and the concentration required for 50% cell death (LC 50 ) were reported for each compound.…”

Section: Bioactivitiesmentioning

confidence: 99%

Recent advances in isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids of marine origin

Nijampatnam

Dutta

Velu

2015

Chinese Journal of Natural Medicines

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The ocean continues to provide a plethora of unique scaffolds capable of remarkable biological applications. A large number of pyrroloiminoquinone alkaloids, including discorhabdins, epinardins, batzellines, makaluvamines, and veiutamine have already been isolated from marine organisms. A class of pyrroloiminoquinone-related alkaloids known as bispyrroloquinones is the focus of this review. This family of marine alkaloids, which contain an aryl substituted bispyrroloquinone ring system, includes three subclasses of alkaloids namely, wakayin, tsitsikammamines A-B and zyzzyanones A-D. Both wakayin and the tsitsikammamines contain a tetracyclic fused bispyrroloiminoquinone ring system, while zyzzyanones contain a fused tricyclic bispyrroloquinone ring system. The unique chemical structures of these marine natural products and their diverse biological properties, including antifungal and antimicrobial activity, as well as the potent, albeit generally nonspecific and universal cytotoxicities, have attracted great interest of synthetic chemists over the past three decades. Tsitsikammamines, wakayin, and several of their analogues show inhibition of topoisomerases. One additional possible mechanism of anticancer activity of tsitsikammamines analogues that was discovered recently is through the inhibition of indoleamine 2,3-dioxygenase, an enzyme involved in tumoral immune resistance. This review discusses the isolation, synthesis, and bioactivities of bispyrroloquinone alkaloids and their analogues.

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“…While there is a very recent report of total synthesis of tsitsikammamine A 36 , there are several other reports available on the synthesis and biological evaluation of the analogs of these alkaloids are available 37,26,2738 .…”

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confidence: 99%

A facile synthesis of bispyrroloquinone and bispyrroloiminoquinone ring system of marine alkaloids

Murugesan¹,

Nadkarni²,

Velu³

2009

Tetrahedron Letters

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Bispyrroloquinone and bispyrroloiminoquinone are two important polycyclic ring systems present in biologically active marine alkaloids such as Zyzzyanones, tsitsikammamines and wakayin. A facile synthesis of these two ring systems starting from a 6-benzylamino indole-4,7-quinone or 6-benzylamino pyrroloiminoquinone is described here. This chemistry involves the construction of a pyrrole ring in a single step by treatment of the starting reagents with ethyl acetoacetate or phenylbutane-1,3-dione in the presence of ceric ammonium nitrate in MeOH/CH2Cl2 solvent.

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Synthesis and in vitro evaluation of imidazole-based wakayin analogues

Abstract: Analogues of wakayin based on diimidazo[1,5,4-de, 1,5,4-h]-quinoxaline have been prepared and evaluated with respect to cytostatic and cytotoxic activity. Assays in a 60-cell-line human cancer panel revealed selective activity against cells with the VEGF (Flt-1) receptor.

Cited by 10 publications

References 23 publications

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Topoisomerase 1B poisons: Over a half‐century of drug leads, clinical candidates, and serendipitous discoveries

Recent advances in isolation, synthesis, and evaluation of bioactivities of bispyrroloquinone alkaloids of marine origin

A facile synthesis of bispyrroloquinone and bispyrroloiminoquinone ring system of marine alkaloids

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