Abstract:
:Diverse indoles and bis-indoles extracted from marine sources have been identified as promising anticancer leads. Herein, we designed and synthesized novel bis-indole series 7a-f and 9a-h as Topsentin and Nortopsentin analogs. Our design is based on replacing the heterocyclic spacer in the natural leads by a more flexible hydrazide linker while sparing the two peripheral indole rings. All the synthesized bis-indoles were examined for their antiproliferative action against human breast cancer (MCF-7 and MDA-MB-231) cell lines. The most potent congeners 7e and 9a against MCF-7 cells (IC50 = 0.44 ± 0.01 and 1.28 ± 0.04 μM, respectively) induced apoptosis in MCF-7 cells (23.7-, and 16.8-fold increase in the total apoptosis percentage) as evident by the externalization of plasma membrane phosphatidylserine detected by Annexin V-FITC/PI assay. This evidence was supported by the Bax/Bcl-2 ratio augmentation (18.65- and 11.1-fold compared to control) with a concomitant increase in the level of caspase-3 (11.7- and 9.5-fold) and p53 (15.4- and 11.75-fold). Both compounds arrested the cell cycle mainly in the G2/M phase. Furthermore, 7e and 9a displayed good selectivity toward tumor cells (S.I. = 38.7 and 18.3), upon testing of their cytotoxicity toward non-tumorigenic breast MCF-10A cells. Finally, compounds 7a, 7b, 7d, 7e, and 9a were examined for their plausible CDK2 inhibitory action. The obtained results (% inhibition range: 16%-58%) unveiled incompetence of the target bis-indoles to inhibit CDK2 significantly. Collectively, these results suggested that herein reported bis-indoles are good lead compounds for further optimization and development as potential efficient anti-breast cancer drugs.
journal_name
Mar Drugsjournal_title
Marine drugsauthors
Eldehna WM,Hassan GS,Al-Rashood ST,Alkahtani HM,A Almehizia A,Al-Ansary GHdoi
10.3390/md18040190subject
Has Abstractpub_date
2020-04-02 00:00:00issue
4issn
1660-3397pii
md18040190journal_volume
18pub_type
杂志文章相关文献
Marine Drugs文献大全abstract::Fucosterol is an algae-derived unique phytosterol having several medicinal properties, including antioxidant, anti-inflammatory, anticholinesterase, neuroprotective, and so on. Accumulated evidence suggests a therapeutic promise of fucosterol in neurodegeneration; however, the in-depth pharmacological mechanism of its...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17110639
更新日期:2019-11-13 00:00:00
abstract::Three new epidithiodiketopiperazines pretrichodermamides D-F (1-3), together with the known N-methylpretrichodermamide B (4) and pretrichodermamide С (5), were isolated from the lipophilic extract of the marine algae-derived fungus Penicillium sp. KMM 4672. The structures of compounds 1-5 were determined based on spec...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md14070122
更新日期:2016-06-27 00:00:00
abstract::The striking rise of methicillin-resistant Staphylococcus aureus (MRSA) infections has become a serious threat to public health worldwide. In an effort to search for new anti-MRSA agents from natural products, a bioassay-guided phytochemical study was conducted on the semi-mangrove plant Myoporum bontioides A. Gray, w...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16110438
更新日期:2018-11-08 00:00:00
abstract::Hepatic fibrosis is an effusive wound healing process, characterized by an excessive deposition of extracellular matrix (ECM), as the consequence of chronic liver injury of any etiology. Current therapeutic repertoire for hepatic fibrosis is limited to withdrawal of the noxious agent, which is not always feasible. Hen...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md13085201
更新日期:2015-08-18 00:00:00
abstract::To sustainably produce marine fish with a high lipid quality rich in omega-3 fatty acids, alternative sources of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are being identified. Moreover, the use of bioactive compounds that would stimulate the in vivo fatty acid synthesis, such as resveratrol (RV), wou...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16100379
更新日期:2018-10-10 00:00:00
abstract::Biologically active compounds with different modes of action, such as, antiproliferative, antioxidant, antimicrotubule, have been isolated from marine sources, specifically algae and cyanobacteria. Recently research has been focused on peptides from marine animal sources, since they have been found as secondary metabo...
journal_title:Marine drugs
pub_type: 杂志文章,评审
doi:10.3390/md10050963
更新日期:2012-05-01 00:00:00
abstract::The vast oceans of the world, which comprise a huge variety of unique ecosystems, are emerging as a rich and relatively untapped source of novel bioactive compounds with invaluable biotechnological and pharmaceutical potential. Evidence accumulated over the last decade has revealed that the diversity of marine microor...
journal_title:Marine drugs
pub_type: 杂志文章,评审
doi:10.3390/md13052924
更新日期:2015-05-13 00:00:00
abstract::Conotoxins in the venom of cone snails (Conus spp.) are a mixture of active peptides that work as blockers, agonists, antagonists, or inactivators of various ion channels. Recently we reported a high-throughput method to identify 215 conotoxin transcripts from the Chinese tubular cone snail, C. betulinus. Here, based ...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md15070228
更新日期:2017-07-18 00:00:00
abstract::In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (2-3), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy-penta-2-enoic acid (AHPEA),...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md11030611
更新日期:2013-02-26 00:00:00
abstract::In this study, the extraction conditions of the crude polysaccharide from Cereus sinensis were optimized by response surface methodology. The optimum extraction conditions were: a ratio of raw material to water volume of 1:80 (g/mL); an extraction temperature of 72 °C; and an extraction time of 3 h. Then, a purified p...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md15050140
更新日期:2017-05-18 00:00:00
abstract::The effect of carrageenans on tomato chlorotic dwarf viroid (TCDVd) replication and symptom expression was studied. Three-week-old tomato plants were spray-treated with iota(ɩ)-, lambda(λ)-, and kappa(κ)-carrageenan at 1 g·L-1 and inoculated with TCDVd after 48 h. The λ-carrageenan significantly suppressed viroid symp...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md13052875
更新日期:2015-05-08 00:00:00
abstract::The geographic position, highly fluctuating sea temperatures and hypersalinity make Persian Gulf an extreme environment. Although this unique environment has high biodiversity dominated by invertebrates, its potential in marine biodiscovery has largely remained untapped. Herein, we aimed at a detailed analysis of the ...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md18070366
更新日期:2020-07-16 00:00:00
abstract::The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated fro...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md12020700
更新日期:2014-01-27 00:00:00
abstract::Spumigins are marine natural products derived from cyanobacteria Nodulariaspumigena, which mimics the structure of the d-Phe-Pro-Arg sequence and is crucial for binding to the active site of serine proteases thrombin and factor Xa. Biological evaluation of spumigins showed that spumigins with a (2S,4S)-4-methylproline...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16110413
更新日期:2018-10-27 00:00:00
abstract::Oxidative stress is the main cause of diabetic nephropathy (DN) progression. Nuclear factor-erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling is a crucial cellular defense system to cope with oxidative stress. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid with remarkable anti...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16040117
更新日期:2018-04-05 00:00:00
abstract::The mucus produced by many marine organisms is a complex mixture of proteins and polysaccharides forming a weak watery gel. It is essential for vital processes including locomotion, navigation, structural support, heterotrophic feeding and defence against a multitude of environmental stresses, predators, parasites, an...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md13085276
更新日期:2015-08-19 00:00:00
abstract::A series of novel cyclic marinopyrroles were designed and synthesized. Their activity to disrupt the binding of the pro-apoptotic protein, Bim, to the pro-survival proteins, Mcl-1 and Bcl-x(L), was evaluated using ELISA assays. Both atropisomers of marinopyrrole A (1) show similar potency. A tetrabromo congener 9 is t...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md12031335
更新日期:2014-03-07 00:00:00
abstract::Tisochrysis lutea is a marine haptophyte rich in omega-3 polyunsaturated fatty acids (e.g., docosahexaenoic acid (DHA)) and carotenoids (e.g., fucoxanthin). Because of the nutraceutical applications of these compounds, this microalga is being used in aquaculture to feed oyster and shrimp larvae. In our earlier report,...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md18110567
更新日期:2020-11-19 00:00:00
abstract::Chemical study of the secondary metabolites of a deep-sea-derived fungus Aspergillus sydowii MCCC 3A00324 led to the isolation of eleven compounds (1-11), including one novel (1) and one new (2) osmane-related monoterpenoids and two undescribed polyketides (3 and 4). The structures of the metabolites were determined b...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md18110561
更新日期:2020-11-17 00:00:00
abstract::Topical administration of drugs into the vagina can provide local therapy of vaginal infections, preventing the possible systemic side effects of the drugs. The natural polysaccharide chitosan is known for its excellent mucoadhesive properties, safety profile, and antibacterial effects, and thus it can be utilized in ...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md18020096
更新日期:2020-01-31 00:00:00
abstract::In this study, as part of our continuous search for environmentally-friendly antifoulants from natural resources, subergorgic acid (SA) was identified from the gorgonian coral Subergorgia suberosa, demonstrating non-toxic, significant inhibitory effects (EC50 1.25 μg/mL, LC50 > 25 μg/mL) against the settlement of Bala...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17020101
更新日期:2019-02-06 00:00:00
abstract::Thirteen nitrogen-containing molecules (1a/1b and 2-12) were isolated from the Indonesian sponge Acanthostrongylophora ingens, highlighting the richness of this organism as a source of alkaloids. Their structures were elucidated using one- and two-dimensional NMR spectroscopy and HR-ESI-MS, while the stereochemistry o...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17080472
更新日期:2019-08-15 00:00:00
abstract::Infection with Helicobacter pylori is a critical cause of gastrointestinal diseases. A crucial host response associated with H. pylori infection includes gastric inflammation, which is characterized by a sustained recruitment of T-helper (Th) cells to the site of infection and distinct patterns of cytokine production....
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17070382
更新日期:2019-06-26 00:00:00
abstract::The methods to obtain chitooligosaccharides are tightly related to the physicochemical properties of the end products. Knowledge of these physicochemical characteristics is crucial to describing the biological functions of chitooligosaccharides. Chitooligosaccharides were prepared either in a single-step enzymatic hyd...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16110430
更新日期:2018-11-02 00:00:00
abstract::Collagenases are the most important group of commercially-produced enzymes. However, even though biological resources are abundant in the sea, very few of these commercially popular enzymes are from marine sources, especially from marine bacteria. We optimized the production of marine collagenases by Pseudoalteromonas...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md15120377
更新日期:2017-12-04 00:00:00
abstract::Microalgae are promising sources for the sustainable production of compounds of interest for biotechnologies. Compared to higher plants, microalgae have a faster growth rate and can be grown in industrial photobioreactors. The microalgae biomass contains specific metabolites of high added value for biotechnology such ...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16030076
更新日期:2018-02-28 00:00:00
abstract::Four new xanthene derivatives, penicixanthenes A-D (1-4), and one known compound 5 were isolated from a marine mangrove endophytic fungus Penicillium sp. JY246 that was obtained from the stem of Ceriops tagal. Their structures were determined by detailed NMR, MS spectroscopic data, modified Mosher's method, and calcul...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17120649
更新日期:2019-11-20 00:00:00
abstract::Sponge-associated bacteria have been mostly cultured from shallow water (≤30 m) sponges, whereas only few studies targeted specimens from below 30 m. This study assessed the cultivability of bacteria from two marine sponges Xestospongia muta and Agelas sventres collected from shallow (<30 m), upper mesophotic (30-60 m...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md17100578
更新日期:2019-10-11 00:00:00
abstract::Six new polyoxygenated cembrane-based diterpenoids, stellatumolides A⁻C (1⁻3), stellatumonins A and B (4 and 5), and stellatumonone (6), were isolated together with ten known related compounds (7⁻16) from the ethyl acetate (EtOAc) extract of soft coral Sarcophyton stellatum. The structures of the new compounds were es...
journal_title:Marine drugs
pub_type: 杂志文章
doi:10.3390/md16060210
更新日期:2018-06-14 00:00:00
abstract::Paralytic shellfish poisoning (PSP), due to saxitoxin and related compounds, typically results from the consumption of filter-feeding molluscan shellfish that concentrate toxins from marine dinoflagellates. In addition to these microalgal sources, saxitoxin and related compounds, referred to in this review as STXs, ar...
journal_title:Marine drugs
pub_type: 杂志文章,评审
doi:10.3390/md20080015
更新日期:2008-06-10 00:00:00