Entity

Time filter

Source Type


Carrasco E.,Institute Biopatologia y Medicina Regenerativa IBIMER | Garcia M.A.,Hospital Universitario Virgen Of Las Nieves | Choquesillo-Lazarte D.,Instituto Andaluz Of Ciencias Of La Tierra Ugr Csic | Garcia-Ruiz J.M.,Instituto Andaluz Of Ciencias Of La Tierra Ugr Csic | Marchal J.A.,Institute Biopatologia y Medicina Regenerativa IBIMER
Current Medicinal Chemistry | Year: 2013

The issue of chiral drug is now a major theme in the design, discovery and development of new drugs. It has been shown for many pharmaceuticals that only one enantiomer contains the desired activity, and the synthesis of such drug molecules in their optically pure form is becoming increasingly important. Mitsunobu reaction was carried out between (R)- and (S)-3,4-dihydro-2H-1,5- benzoxathiepin-3-ol and purines under microwave irradiation. A contraction into a six-membered ring takes place with concomitant inversion at the stereocentre with excellent enatiomeric excesses giving rise to the homochiral 9-(2,3-dihydro-1,4-benzoxathiin-3-ylmethyl)-9H-purines. The anti-tumour activity of all enantiomers is reported against the caspase-3-deficient MCF-7 and the wild type SKBR-3 human breast cancer cells. The most active homochiral compound displays an IC50 of 1.85 μM and induces inhibition of the translation initiation factor eIF2α. All homochiral compounds included in this study show different apoptotic effects between both enantiomers with levels up to 99%. We have analyzed caspase-mediated apoptotic pathways on enantiomers and racemates. We have found a homochiral derivative that activates the canonical intrinsic caspase-8/caspase-3 apoptotic pathway on the MCF-7 cells, and a racemic compound that induces caspase-2 activation. Moreover, we demonstrate the involvement of caspase activation during cell death induced by these compounds in SKBR-3 cells. © 2013 Bentham Science Publishers. Source


Chayboun I.,Abdelmalek Essaadi University | Boulifa E.,Abdelmalek Essaadi University | Mansour A.I.,Abdelmalek Essaadi University | Rodriguez-Serrano F.,Institute Biopatologia y Medicina Regenerativa IBIMER | And 4 more authors.
Journal of Natural Products | Year: 2015

The first enantiospecific syntheses of neopetrosiquinones A (6) and B (7), two merosesquiterpenes isolated from the deep-water sponge Neopetrosia cf. proxima, from the labdane diterpene trans-communic acid (10) have been achieved. A key step of the synthetic sequence is the simultaneous aromatization of the C ring and the benzylic oxidation on C-7 of an advanced intermediate, mediated by the oxygen-DDQ system. The in vitro antiproliferative activities of neopetrosiquinone B (7) and of the synthetic intermediates 8 and 9 against human breast (MCF-7), lung (A-549), and colon (T-84) tumor cell lines have been assayed. The most potent was compound 9 (IC50 = 4.1 μM), which was twice as active as natural compound 7 (IC50 = 8.3 μM) against A-549 cells. In addition, the treatment with these compounds resulted in an induction of apoptosis. These findings indicate that the terpene benzoquinones reported here might be potentially useful as anticancer agents. © 2015 The American Chemical Society and American Society of Pharmacognosy. Source


Marchal J.A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Boulaiz H.,Institute Biopatologia y Medicina Regenerativa IBIMER | Garcia M.A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Garcia M.A.,Hospital Universitario Virgen Of Las Nieves | And 7 more authors.
European Journal of Medicinal Chemistry | Year: 2011

Completing an SAR study, a series of (RS)-6-substituted-7- or 9-(1,2,3,5-tetrahydro-4,1-benzoxazepine-3-yl)-7H or 9H-purines has been prepared under microwave-assisted conditions. Their antiproliferative activities on MCF-7 and MDA-MB-231 cancerous cell lines are presented, being the majority of the IC50 values below 1 μM. The most active compound (RS)-2,6-dichloro-9-[1-(p-nitrobenzenesulfonyl)-1,2,3,5-tetrahydro-4, 1-benzoxazepin-3-yl]-9H-purine (14) presents an IC50 of 0.166 μM against the human cancerous cell line MDA-MB-231. Compound 14 was the most selective against the human breast adenocarcinoma MCF-7 and MDA-MB-231 cancer cell lines (Therapeutic Indexes, TIs = 5.1 and 11.0, respectively) in relation to the normal one MCF-10A. (RS)-14 was resolved into its enantiomers. Both enantiomers are equally potent, but more potent than the corresponding racemic mixture. (R)-14 induces apoptosis against MCF-7 up to 52.50% of cell population after 48 h, being more potent than the clinical-used drug paclitaxel (43%). (RS)-14 induces no acute toxicity in mice after two weeks of treatment. Source


Marchal J.A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Ramirez A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Garcia M.A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Garcia M.A.,Universitario Virgen Of Las Nieves | Aranega A.,Institute Biopatologia y Medicina Regenerativa IBIMER
European Journal of Medicinal Chemistry | Year: 2011

Herein are reported the synthesis and anticancer activity against the human breast cancer cell line MCF-7 of a series of substituted (RS)-9-(2,3-dihydro-1, 4-benzoxathiin-2-ylmethyl)-9H-purine derivatives and (RS)-9-(2,3-dihydro-1,4- benzodioxin-2-ylmethyl)-9H-purine derivatives. When the Mitsunobu reaction was carried out between (RS)-2,3-dihydro-1,4-benzoxathiin-3-methanol and the heterocyclic bases 6-chloro-, 2,6-dichloro, and 6-bromo-purines under microwave-assisted conditions, a formal 1,4-sulfur migration takes place through two consecutive oxyranium and episulfonium rings, giving rise to the corresponding (RS)-9-(2,3-dihydro-1,4-benzodioxin-3-ylmethyl)-9H-purine derivatives, previously reported by us. The most active compound (RS)-2,6-dichloro-9-(2,3-dihydro-1,4-benzoxathiin-2-ylmethyl)-9H-purine shows an IC 50 = 2.75 ± 0.02 μM. When the cancerous cells were treated with this compound, a significant increase of apoptotic cells (70.08 ± 0.33%) was obtained in relation to the control ones. The induction of the G 2/M cell cycle arrest and apoptosis by the three most active compounds is associated with increased phosphorylation of eIF2α in human breast cancer cells. © 2011 Elsevier Masson SAS. All rights reserved. Source


Morales F.,University of Granada | Ramirez A.,Institute Biopatologia y Medicina Regenerativa IBIMER | Ramirez A.,University of Jaen | Conejo-Garcia A.,University of Granada | And 3 more authors.
European Journal of Medicinal Chemistry | Year: 2014

As leads we took several benzo-fused seven- and six-membered scaffolds linked to the pyrimidine or purine moieties with notable anti-proliferative activity against human breast, colon and melanoma cancerous cell lines. We then decided to maintain the double-ringed nitrogenous bases and change the other components to the ethyl acetate moiety. This way six purine and two 5-fluorouracil derivatives were obtained and evaluated against the MCF-7, HCT-116, A-375 and G-361 cancer cell lines. Two QSARs are obtained between the anti-proliferative IC50 values for compounds 26-33 and the clog P against the melanoma cell lines A-375 and G-361. Our results show that two of the analogues [ethyl 2-(2,6-dichloro-9H- or 7H-purine-9- or 7-yl)acetates (30 and 33, respectively)] are potent cytotoxic agents against all the tumour cell lines assayed, showing single-digit micromolar IC50 values. This exemplifies the potential of our previously reported purine compounds to qualify as lead structures for medicinal chemistry campaigns, affording simplified analogues easy to synthesize and with a noteworthy bioactivity. The selective activity of 30 and 33 against the melanoma cell line A-375, via apoptosis, supposes a great advantage for a future therapeutic use. © 2014 Elsevier Masson SAS. All rights reserved. Source

Discover hidden collaborations