1,721,229 research outputs found
Synthesis of natural products as novel antibacterial agents
No full textAn overview of recently synthesized natural compounds endowed with antimicrobial activity is reported
Research progress on Camptothecin analogues as Topoisomerase inhibitors
No full textNatural products, with their tremendous structural diversity, are an important source of new biologically active compounds. Many useful drugs are of natural origin, or are obtained by skilful modification of natural substances. Various important anti-cancer agents like vincristine, vinblastin, paclitaxel and podophyllotoxin have been isolated from various plant sources.
Camptothecin (CPT), a pentacyclic alkaloid first isolated by Wall et al. in 1966 from the Chinese tree Camptotheca acuminata,1 was found to possess an interesting antitumor activity. Late in 1985, it was reported by Liu et al. that the cytotoxic activity of CPT was attributed to a novel mechanism of action involving the nuclear enzyme classified as type I DNA topoisomerase.2 Topoisomerase I is an ubiquitous enzyme that plays an important role in DNA replication, transcription, recombination and repair. Thus, inhibition of topoisomerase I has important consequences for chemotherapeutic treatment of tumors.
Camptothecin has a broad spectrum of anticancer activities, however its low solubility in water, the lactone ring instability and high toxicity, including myelosuppression, vomiting, diarrhoea and serious hemorrhagic cystitis, severely limited its clinical use. These adverse effects led to a growing interest in the development of CPT analogues that exhibit less severe drawbacks, while maintaining their therapeutic activity.
Fifty years after its discovery, extensive efforts continue to be made in the medicinal chemistry of camptothecin. Thousands of CPT analogues have been prepared and structure-activity relationship studies have been developed. Some analogues are in various stages of preclinical and clinical development; two of them, topotecan and irinotecan, have successfully entered into the market and are used as topoisomerase I poisons in clinical practice.3
Besides structural modification, the establishment of new drug delivery systems has recently become a hot topic in the CPT research. Progresses in the delivery systems, in controlled release systems and targeting delivery systems of camptothecins are the great challenge of this last decade.
The main focus of this presentation will be on the development of CPT derivatives over the years (included those from our own research) and the potential and future development trend of the newly discovered anticancer compounds.
References
1. Wall, M.E.; Wani, M.C.; Cooke, C.E.; Palmer; K.T.; McPhail; A.T.; Sim, G.A. J. Am. Chem. Soc. 1966, 88, 3888.
2. Hsiang, Y.-H.; Hertzberg, R.; Hecht, S.M.; Liu, L.F. J. Biol. Chem. 1985, 260, 14873.
3. Dallavalle S.; Merlini, L. in “Modern Alkaloids”; E. Fattorusso, O. Tagliatatela Eds.; Wiley-VCH: Weinheim, 2008, pp. 503-520
Approach to synthesis of the natural compound Leopolic Acid A
No full textLeopolic Acid A (1) has recently been isolated from a terrestrial-derived Streptomyces sp isolated from the rhizosphere of the plant Juniperus excels collected from Ukraine.1 It possesses a rare ureido dipeptide Phe-CO-Val attached to 5-dihydro-3-hydroxy-pyrrole-2-one ring.
Ureido-peptides with varying number of amino acids have been previously isolated from actinomycetes ann show intesting biological activities. Noteworthy examples include the microbial alkaline protease inhibitors, (MAPI)-a and b, GE20372 factor A and B, as HIV-1 protease inhibitors, and the pacidamycins, exhibiting anti-Pseudomonas aeruginosa
The unprecedented structural features of Leopolic acid, consisting of an aliphatic side chain attached to the novelpyrrole-2-one residue connected to the ureido dipeptide, prompted us to develop a synthetic strategy of this naturally occurring compound.
The proposed methodology is centred on the condensation of .the 4-substituted 3-hydroxy-1,5-dihydropyrrol-2-one (2) and the ureido dipeptide moiety (3)
A new synthesis of the cytotoxic alkaloid Luotonine A
No full textA convenient synthesis of the cytotoxic alkaloid Luotonine A has been achieved using cheap and readily accessible reagents. The key intermediate in the synthesis is the tricyclic compound 2,3-dihydro[1H]-pyrrolo[3,4-b]quinolin-3-one (5)
Efficient Synthesis of 3,7-Diaryl-1,4-dihydro[1,2,4]triazolo[5,1-c][1,2,4]triazines
No full textAn efficient and versatile protocol for the synthesis of novel 3,7-diaryl-substituted 1,4-dihydro[1,2,4]triazolo[5,1-c][1,2,4]triazines is described, via alkylation/cyclization of 3,5-dibromo-1H-1,2,4-triazole, followed by Suzuki coupling with arylboronic acids
A synthetic approach to 3-acyltetramic acid and application to the total synthesis of Epicoccamide D
No full textNaturally accoutring 3-acyltetramic acids1,2 (3-acylpyrrolodin-2,4diones, 1) are core structural skeletons that have been found in various biological active products, such as magnesidin A(antibiotic activity)3a, tenuazonic acid (antiviral and antitumor activity)3b, Sch 213766 (anti-HIV activity)3C, the melophlins (antitumor activity)3d, and the macrocidins ( herbicidal activity). 3f Three new tetramic acid derivatives, epicoccamides B-D, have recently been isolated from an Epicoccum sp. associated with the tree fungus Pholiota squarrosa. The derivative with the longest chain, epicoccamide D, induces morphogenesis and pigment formation in surface cultures of fungus Phoma destructive at concentration of 1.7nM. Despite the great significance of 3-acyltetramic acids, the development of a comprehensive and general protocol for the synthesis of this type of compounds has substantially not been achieved.4-10
We have developed an efficient synthetic sequence for the construction of N-methyl- 3-acylteramic acids. The strategy was applied to the synthesis of the natural compound Epicoccamid
Approach to the synthesis of the natural compound Leopolic acid A
No full textLeopolic Acid A (1) has recently been isolated from a terrestrial-derived Streptomyces sp isolated from the rhizosphere of the plant Juniperus excels collected from Ukraine. It possesses a rare ureido dipeptide Phe-CO-Val attached to 5-dihydro-3-hydroxy-pyrrole-2-one ring.
Ureido-peptides with varying number of amino acids have been previously isolated from actinomycetes and show intesting biological activities. Noteworthy examples include the microbial alkaline protease inhibitors, (MAPI)-a and b, GE20372 factor A and B, as HIV-1 protease inhibitors, and the pacidamycins, exhibiting anti-Pseudomonas aeruginosa activity.
The unprecedented structural features of Leopolic acid, consisting of an aliphatic side chain attached to the novel pyrrole-2-one residue connected to the ureido dipeptide, prompted us to develop a synthetic strategy of this naturally occurring compound.
The proposed methodology is centred on the condensation of .the 4-substituted 3-hydroxy-1,5-dihydropyrrol-2-one and the ureido dipeptide moiet
Reazione intramolecolare di Friedel-Crafts di indoli con gruppi carbonilici : una semplice sintesi di b-carbolin-1-oni e di diidro-2H-azepino[3,4-b]indol-1-oni
No full textFirst Total Synthesis of Topopyrone C
No full textThe first synthesis of topopyrone C, a natural compound and inhibitor of Topoisomerase I, has been carried out by Marschalk alkylation of 1-hydroxy-3,6,8-trimethoxyanthraquinone, followed by a Baker–Venkataraman chain elongation and an acid-catalyzed cyclization for the construction of the pyrone ring
- …
