- Flexible Construction of Functionalized-Pyrroles under Palladium or Copper Catalysis in the Presence of BF3 ? Et2O
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We have developed a flexible approach enabling the access to highly functionalized pyrroles under palladium or copper catalysis in the presence of BF3 ? Et2O. This catalytic methodology utilizes commercially available amines as react
- Guo, Wusheng,Liu, Teng,Liu, Yin,Wei, Kun,Yan, Biwei
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supporting information
(2022/01/26)
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- Design, synthesis and in-vitro anti-cancer evaluation of novel derivatives of 2-(2-methyl-1,5-diaryl-1h-pyrrol-3-yl)-2-oxo-n-(pyridin-3-yl)acetamide
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Objective: Several anti-tubulin agents were introduced for the cancer treatment so far. Despite successes in the treatment of cancer, these agents cause toxic side effects, including peripheral neuropathy. Comparing anti-tubulin agents, indibulin seemed to cause minimal peripheral neuropathy, but its poor aqueous solubility and other potential clinical problems have led to its remaining in a preclinical stage. Methods: Herein, indibulin analogues were synthesized and evaluated for their in vitro anti-cancer activity using MTT assay (on the MCF-7, T47-D, MDA-MB231 and NIH-3T3 cell lines), annexin V/PI staining assay, cell cycle analysis, anti-tubulin assay and caspase 3/7 activation assay. Results: One of the compounds, 4a, showed good anti-proliferative activity against MCF-7 cells (IC50: 7.5 μM) and low toxicity on a normal cell line (IC50 > 100μM). All of the tested compounds showed lower cytotoxicity on normal cell line in comparison to reference compound, indibulin. In the annexin V/PI staining assay, induction of apoptosis in the MCF-7 cell line was observed. Cell cycle analysis illustrated an increasing proportion of cells in the sub-G-1 phase, consistent with an increasing proportion of apoptotic cells. No increase in G2/M cells was observed, consistent with the absence of anti-tubulin activity. A caspase 3/7 assay protocol showed that apoptosis induction by more potent compounds was due to activation of caspase 3. Conclusion: newly synthesized compounds exerted acceptable anticancer activity and further investigation of current scaffold would be beneficial.
- Alipour, Mohsen,Amini, Mohsen,Hamel, Ernest,Hosseinkhani, Saman,Moghadam, Ebrahim Saeedian,Ostad, Seyednasser,Saravani, Farhad,Shahsavari, Zahra
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p. 340 - 349
(2020/04/17)
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- Synthesis and anti-breast cancer activity of novel indibulin related diarylpyrrole derivatives
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Background: During recent years, a number of anti-tubulin agents were introduced for treatment of diverse types of cancer. Despite their potential in the treatment of cancer, drug resistance and adverse toxicity, such as peripheral neuropathy, are some of the negative effects of anti-tubulin agents. Among anti-tubulin agents, indibulin was found to cause minimal peripheral neuropathy. Thus far, however, indibulin has not entered clinical usage, caused in part by its poor aqueous solubility and other developmental problems in preclinical evaluation. Objectives: With respect to need for finding potent and safe anticancer agents, in our current research work, we synthesized several indibulin-related diarylpyrrole derivatives and investigated their anti-cancer activity. Methods: Cell cultur studies were perfomred using the MTT cell viability assay on the breast cancer cell lines MCF-7, T47-D, and MDA-MB231 and also NIH-3?T3 cells as representative of a normal cell line. The activity of some of the synthesized compounds for tubulin interaction was studied using colchicine binding and tubulin polymerization assays. The annexin V-FITC/PI method and flow cytometric analysis were used for studying apoptosis induction and cell cycle distribution. Results and conclusion: Two of the synthesized compounds, 4f and 4?g, showed high activity on the MDA-MB231 cell line (IC50?= 11.82 and 13.33?μM, (respectively) and low toxicity on the normal fibroblast cells (IC50?> 100?μM). All of the tested compounds were more potent on T47-D cancer cells and less toxic on NIH-3?T3 normal cells in comparison to reference compound, indibulin. The tubulin polymerization inhibition assay and [3H]colchicine binding assay showed that the main mechanism of cell death by the potent synthesized compounds was not related to an interaction with tubulin. In the annexin V/PI staining assay, the induction of apoptosis in the MCF-7 and MDA-MB231 cell lines was observed. Cell cycle analysis illustrated an increased percentage of sub-G-1 cells in the MDA-MB231 cell line as a further indication of cell death through induction of apoptosis. [Figure not available: see fulltext.].
- Saeedian Moghadam, Ebrahim,Hamel, Ernest,Shahsavari, Zahra,Amini, Mohsen
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p. 179 - 189
(2019/03/26)
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- Switching on the activity of 1,5-diaryl-pyrrole derivatives against drug-resistant ESKAPE bacteria: Structure-activity relationships and mode of action studies
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Antibiotic resistance represents a major threat worldwide. Gram-positive and Gram-negative opportunistic pathogens are becoming resistant to all known drugs mainly because of the overuse and misuse of these medications and the lack of new antibiotic development by the pharmaceutical industry. There is an urgent need to discover structurally innovative antibacterial agents for which no pre-existing resistance is known. This work describes the identification, synthesis and biological evaluation of a novel series of 1,5-diphenylpyrrole compounds active against a panel of ESKAPE bacteria. The new compounds show high activity against both wild type and drug-resistant Gram + ve and Gram-ve pathogens at concentrations similar or lower than levofloxacin. Microbiology studies revealed that the plausible target of the pyrrole derivatives is the bacterial DNA gyrase, with the pyrrole derivatives displaying similar inhibitory activity to levofloxacin against the wild type enzyme and retaining activity against the fluoroquinolone-resistant enzyme.
- Masci, Domiziana,Hind, Charlotte,Islam, Mohammad K.,Toscani, Anita,Clifford, Melanie,Coluccia, Antonio,Conforti, Irene,Touitou, Meir,Memdouh, Siham,Wei, Xumin,La Regina, Giuseppe,Silvestri, Romano,Sutton, J. Mark,Castagnolo, Daniele
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p. 500 - 514
(2019/06/18)
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- Design and Synthesis of 1-((1,5-Bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine (BM212) and N-Adamantan-2-yl-N′-((E)-3,7-dimethylocta-2,6-dienyl)ethane-1,2-diamine (SQ109) Pyrrole Hybrid Derivatives: Discovery of Potent Antitubercular Agents Effective against Multidrug-Resistant Mycobacteria
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Novel pyrroles have been designed, synthesized, and evaluated against mycobacterial strains. The pyrroles have originally been designed as hybrids of the antitubercular drugs BM212 (1) and SQ109 (2), which showed common chemical features with very similar topological distribution. A perfect superposition of the structures of 1 and 2 revealed by computational studies suggested the introduction of bulky substituents at the terminal portion of the pyrrole C3 side chain and the removal of the C5 aryl moiety. Five compounds showed high activity toward Mycobacterium tuberculosis, while 9b and 9c were highly active also against multidrug-resistant clinical isolates. Compound 9c showed low eukaryotic cell toxicity, turning out to be an excellent lead candidate for preclinical trials. In addition, four compounds showed potent inhibition (comparable to that of verapamil) toward the whole-cell drug efflux pump activity of mycobacteria, thus turning out to be promising multidrug-resistance-reversing agents.
- Bhakta, Sanjib,Scalacci, Nicolò,Maitra, Arundhati,Brown, Alistair K.,Dasugari, Saiprasad,Evangelopoulos, Dimitrios,McHugh, Timothy D.,Mortazavi, Parisa N.,Twist, Alexander,Petricci, Elena,Manetti, Fabrizio,Castagnolo, Daniele
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p. 2780 - 2793
(2016/04/10)
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- Synthesis of furans, pyrroles and pyridazines by a ruthenium-catalysed isomerisation of alkynediols and in situ cyclisation
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Alkyne-1,4-diols are readily available substrates which are isomerised to 1,4-diketones using Ru(PPh3)3(CO)H2/xantphos as a catalyst. In situ cyclisation into furans, pyrroles and pyridazines has been achieved under suitable conditions.
- Pridmore, Simon J.,Slatford, Paul A.,Taylor, James E.,Whittlesey, Michael K.,Williams, Jonathan M.J.
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supporting information; experimental part
p. 8981 - 8986
(2009/12/27)
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- Ruthenium-catalysed conversion of 1,4-alkynediols into pyrroles
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Various 1,2,5-substituted pyrroles have been synthesised from 1,4-alkynediols using a ruthenium catalysed isomerisation to give the corresponding 1,4-dicarbonyl compounds, which undergo in situ cyclisation to pyrroles in the presence of amine.
- Pridmore, Simon J.,Slatford, Paul A.,Daniel, Aurélie,Whittlesey, Michael K.,Williams, Jonathan M.J.
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p. 5115 - 5120
(2008/02/09)
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- New pyrrole derivatives as antimycobacterial agents analogs of BM212
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During the course of our investigations in the field of azole antimicrobial agents, we have identified BM212 a pyrrole derivative with good in vitro activity against mycobacteria and candidae. These findings prompted us to prepare new pyrrole derivatives
- Biava, Mariangela,Fioravanti, Rossella,Porretta, Giulio Cesare,Deidda, Delia,Maullu, Carlo,Pompei, Raffaello
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p. 2983 - 2988
(2007/10/03)
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- Synthesis and antimicrobial activity of some 1,5-diaryl-2-methyl-3-carbethoxy-4-(4-methyl-piperazin-1-ylmethyl)-pyr roles and some 1,5-diaryl-2-methyl-3,4-di(4-methyl-piperazin-1-ylmethyl)-pyrroles
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The synthesis and anti-Candida activity of some 1,5-diarylpyrrole derivatives are reported and some structure-activity relationships are proposed.
- Cerreto,Scalzo,Villa
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p. 1735 - 1746
(2007/10/02)
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- Studies on anti-Candida agents with a pyrrole moiety. Synthesis and microbiological activity of some 3-aminomethyl-1,5-diaryl-2-methyl-pyrrole derivatives
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The synthesis and anti-Candida activity of some 3-aminomethyl-1,5-diaryl-2-methyl-pyrrole derivatives are reported. Some derivatives show a rather strong anti-Candida activity. On the basis of experimental results, microbiological activity of 1,5-diarylpy
- Cerreto,Villa,Retico,Scalzo
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p. 701 - 708
(2007/10/02)
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