Synthesis and antitumor properties of 2,5-bis(3′-indolyl)thiophenes: Analogues of marine alkaloid nortopsentin

Diana, Patrizia; Carbone, Anna; Barraja, Paola; Montalbano, Alessandra; Martorana, Annamaria; Dattolo, Gaetano; Gia, Ornella; Via, Lisa Dalla; Cirrincione, Girolamo

doi:10.1016/j.bmcl.2007.01.065

Cited by 94 publications

(37 citation statements)

References 12 publications

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“…Earlier liquid chromatography-mass spectrometry (LC-MS) analysis indicated that nortopsentin A was present as the major component of the active fraction from this organism (7). Nortopsentin A is a bis(indolyl)imidazole alkaloid with antiinflammatory and antitumor properties that has been previously identified from related specimens of Spongosorites (8,9) and has never been tested for antiplasmodial activity.…”

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confidence: 99%

The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity

Alvarado

Roberts

Wright

et al. 2013

Antimicrob Agents Chemother

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A library of enriched marine natural product fractions was screened for their antiplasmodial activity using a SYBR green I fluorescence-based assay. Fractions derived from a sponge of the genus Spongosorites exhibited potent inhibition of Plasmodium falciparum growth. This genus of sponge has been reported to contain the nortopsentin and topsentin class of bis-indole imidazole alkaloids. This is the first report of nortopsentin A inhibiting parasite growth at the trophozoite stage at submicromolar 50% inhibitory concentrations (IC 50 ). Over 300 million clinical cases of malaria occur annually, resulting in more than 1 million deaths (1). Unfortunately, because of the prevalence of drug-resistant malaria parasite strains, existing drugs are increasingly losing their efficacy. Therefore, there is an urgent need to identify new drug leads to reduce the global malaria burden. Marine biological diversity provides an excellent opportunity to identify novel drug leads from secondary metabolites of marine organisms. Although research aiming to discover novel marine-derived antiplasmodial agents is relatively recent, over 60 active compounds have been reported to date (2). One of the more important leads is manzamine A, a structurally complex ␤-carboline alkaloid isolated from a Haliclona sp. Manzamine A cleared 90% of the parasite burden in P. berghei-infected mice with a single intraperitoneal dose (3, 4). Unfortunately, toxicity issues have limited the clinical development of the compound.A library of enriched chemical fractions derived from marine organisms collected at depths greater than 50 m was prepared at Harbor Branch Oceanographic Institute using medium-pressure liquid chromatography on an ISCO Combiflash purification system. These materials were screened for their ability to inhibit the chloroquine-sensitive P. falciparum strain 3D7 and the chloroquine-resistant strain Dd2. The enriched fractions were solubilized in ethanol and, when necessary, further diluted in culture medium for assay. The inhibitory properties of the library were evaluated at 5 g/ml using a SYBR green I assay (5, 6) with the chloroquine-sensitive P. falciparum strain 3D7 (1% parasitemia)

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confidence: 99%

The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity

Alvarado

Roberts

Wright

et al. 2013

Antimicrob Agents Chemother

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“…At first, we investigated the enhancing effect on Am80-induced HL-60 cell differentiation of DIM (1), its derivative 6 and positional isomers of DIM (22,25). HL-60 cell differentiation was assayed by the use of nitroblue tetrazolium (NBT) reduction assay, as described previously.…”

Section: Effects On Hl-60 Cell Differentiationmentioning

confidence: 99%

Enhancement of Chemically-Induced HL-60 Cell Differentiation by 3,3'-Diindolylmethane Derivatives

Noguchi‐Yachide

Tetsuhashi

Aoyama

et al. 2009

CHEMICAL & PHARMACEUTICAL BULLETIN

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3,3Ј-Diindolylmethane (DIM, 1) is a major metabolite (spontaneously formed product in intragastric acid condition) of indole-3-carbinol (I3C, 2) which is a phytochemical expressed in brassica vegetables, including broccoli, brussels sprouts, kales and the cabbages, and has been thought to be associated with the anticancer/cancer chemopreventive activities of vegetable consumption.1) DIM (1) controls proliferation of various tumor cells, including cells of breast cancer, prostate cancer, ovary cancer, lung cancer and pancreatic cancer, by inducing G 1 /S arrest of the cell cycle and apoptosis.2) In addition, DIM (1) modulates metabolism of estrogen and testosterone, 3,4) which act as indigenous tumor promoters for several hormone-dependent cancers. DIM (1) is also reported to be a weak agonist for the arylhydrocarbon receptor (AhR) and blocks the effects of estrogens via inhibition of AhR-estrogen receptor cross talk.5) In addition, DIM (1) possesses other various activities, including immunomodulatory effect.6) All the experimental studies suggest that DIM (1) has incredible potential both for prevention and for treatment of cancer.Although the molecular basis of cancer chemopreventive and cancer chemotherapic effects of DIM (1) is unclear, effects of DIM (1) on cell differentiation would be one of candidate mechanisms underlying the biological activities elicited by DIM (1). In fact, Kim et al. recently reported that indirubin, another AhR agonist with a structure related to that of DIM (1), and its derivatives show enhancing effect on 1,25-dihydroxyvitamin D 3 (1,25-VD 3 )-and all-trans retinoic acid (ATRA)-induced cell differentiation of HL-60 leukemia cells. 7)Under such circumstances, we investigated the enhancing effect on chemically-induced HL-60 cell differentiation of DIM (1) and its derivatives in combination with various cell differentiation inducers, including ATRA, tamibarotene (Am80, 3), 1,25-VD 3 , 12-O-tetradecanoyl phorbol-13-acetate (TPA) and dimethyl sulfoxide (DMSO). All of these chemicals are known to induce terminal differentiation in leukemic cell lines, including HL-60 and U937 cells. ATRA and Am80 are therapeutic agents for acute promyelocytic leukemia (APL) and induce differentiation of HL-60 cells to mature granulocytes.8) On the other hand, 1,25-VD 3 and TPA have been established to induce differentiation of HL-60 cells to mature monocytes. 9) DMSO is another typical cell differentiation inducer. 10) Results and DiscussionChemistry DIM (1), its derivatives (4-17), and isomers of DIM [2,2Ј-DIM (22) and 2,3Ј-DIM (25) Bunkyo-ku, Tokyo 113-0032, Japan. Received January 8, 2009; accepted February 19, 2009; published online February 24, 2009 3,3-Diindolylmethane (DIM, 1) and its derivatives have been prepared, and their enhancing effects on chemically-induced HL-60 cell differentiation were analyzed. Among the prepared compounds, IndDIM (12) showed the most potent enhancing effect on HL-60 cell differentiation induced by chemicals, including retinoids, 1,25-dihydroxyvitamin D 3 , 12-O-...

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“…Due to the interesting biological activities, different analogues of the marine nortopsentins have been synthesized in which the imidazole moiety of the nortopsentin was replaced by five-or six-membered heterocyclic rings such as thiazole Carbone et al, 2015Carbone et al, , 2013Carbone et al, 2014), pyrazinone (Jiang and Gu, 2000), pyrimidines, pyrazines , thiophenes (Diana et al, 2007a), pyridines , pyrazoles (Diana et al, 2007b) and 1,2,4-thiadiazoles which were reported for their cytotoxicity against several cancer cell lines.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study

Choppara

Bethu

Prasad

et al. 2019

Arabian Journal of Chemistry

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Two series of novel bis(indole) analogues viz., N 0 -((5-substituted-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)alkanehydrazides (7a-f) and N 0 -((5-substituted-1-(3-methylbut-2-e nyl)-1H-indol-3-yl)methylene)-n-(1H-indol-3-yl)acetohydrazide (8a-f) were synthesized and characterized by spectral analysis. The target molecules were screened for their antimicrobial, anticancer activities and structure and activity relationship (SAR) was investigated. Compounds 7a, 7c and 8a were found to be active in antimicrobial screening. Anticancer screening reveals that Compound 7c was active against HeLa cell line with an IC 50 of 43.1 lM and compound 7d was found to be interesting candidate with an IC 50 of 26.0 and 30.2 lM against Colo-205 and Hep G2 cell lines respectively. ª 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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Synthesis and antitumor properties of 2,5-bis(3′-indolyl)thiophenes: Analogues of marine alkaloid nortopsentin

Cited by 94 publications

References 12 publications

The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity

The Bis(Indolyl)Imidazole Alkaloid Nortopsentin A Exhibits Antiplasmodial Activity

Enhancement of Chemically-Induced HL-60 Cell Differentiation by 3,3'-Diindolylmethane Derivatives

Synthesis, characterization and cytotoxic investigations of novel bis(indole) analogues besides antimicrobial study

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