Indolocarbazole
Indolocarbazoles (ICZs) are a class of compounds that are under current study due to their potential as anti-cancer as well as antimicrobial drugs and the prospective number of derivatives and uses found from the basic backbone alone.Due to the extensive number of structures available, this review will focus on the more important groups here while covering their occurrence, biological activity, biosynthesis, and laboratory synthesis.The first isolated ICZ, dubbed staurosporine (STA) was in 1977 from a culture of Streptomyces staurosporeus found in a soil sample from Iwate Prefecture, Japan.Over the course of the next decade, further study of the compound showed some fungal inhibition, hypotensive activity, and most importantly, a broad protein kinase inhibitor.Some of the strains from which ICZ compounds have been found are Actinomadura melliaura in Bristol Cove, San Diego County, California, Streptomyces hygroscopicus in Numazu Prefecture, Japan, Micromonospora sp.Nostoc sphaericum from Manoa Hawaii, Tolypothrix tjipanasensis from Vero Beach, Florida, and Fischerella ambigua strain 108b from Leggingen, Switzerland.[6] One of the major lessons learned from initial research on STA was the development of the pharmacophore model for a protein kinase inhibitor in which a bidentate hydrogen donating system flanked by various hydrophobic groups inserts into the binding site.[27] Ever since the birth of ICZ research in the late seventies, the field has been burgeoning with continued advances in both technology and organic chemistry techniques.While only a handful of ICZ based compounds have made it past stage II clinical trials, the sheer variety that these molecules can take on leaves much still unexplored territory.Of particular recent interest in synthesis techniques is the use of palladium based catalysts, which have been found to be excellent activators for use in formation of carbon-carbon bonds.
Structural formulastaurosporinealkaloidstereochemistryrebeccamycinPanamaleukemiamelanomaadenocarcinomaSan Diego County, CaliforniaStreptomyces hygroscopicusFuerteventura IslandShandongactinomycetesslime moldscyanobacteriaLycogala epidendrummyxomycetesArcyriaKochi PrefectureNostocVero Beach, FloridaFischerellatunicatemolluskflatwormspongeprotein kinasesDNA topoisomerasepharmacophoreTopoisomeraseStreptomyces griseusdirecthost-directedhuman cytomegalovirusStaphylococcus aureusMycobacterium abcessustryptophanglycosylationenediynecalicheamicinpalladiumBibcodeCenter for Pharmaceutical Research and Innovationchemotherapeutic agentsantineoplastic agentsM phasemicrotubuleVinca alkaloidsVinblastineVincristineVindesineVinflunineVinorelbineTaxanesCabazitaxelDocetaxelLarotaxelOrtataxelPaclitaxelTesetaxelEpothilonesIxabepiloneDNA replicationantimetabolitesS phaseFolic acidDihydrofolate reductase inhibitorAminopterinMethotrexatePemetrexedPralatrexateThymidylate synthase inhibitorRaltitrexedPurineAdenosine deaminase inhibitorPentostatinHalogenatedribonucleotide reductase inhibitorsCladribineClofarabineFludarabineNelarabineRabacfosadineThiopurineMercaptopurineTioguaninePyrimidineCapecitabineCarmofurDoxifluridineFloxuridineFluorouracilTegafur+gimeracil/oteracilDNA polymerase inhibitorCytarabine+daunorubicinRibonucleotide reductase inhibitorGemcitabineHypomethylating agentAzacitidineDecitabineDeoxyribonucleotideHydroxycarbamideTopoisomerase inhibitorsCamptothecaBelotecanCamptothecinEtirinotecan pegolExatecanIrinotecanLurtotecanRubitecanTopotecanPodophyllumEtoposideTeniposideIntercalationAnthracyclinesAclarubicinAmrubicinDaunorubicin+cytarabineDoxorubicinEpirubicin