Plant natural products: Back to the future or into extinction?

McChesney, James D.; Venkataraman, Sylesh K.; Henri, John T.

doi:10.1016/j.phytochem.2007.04.032

Cited by 316 publications

(216 citation statements)

References 34 publications

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“…16 Limited sustainable supply of most bioactive natural products is the main obstacle that may hinder further development as drug leads. [17][18][19] Feasible regioselective and cost effective synthesis of the pharmacologically active marine natural product 1 not only secured adequate supply for in vitro and animal studies but it also allowed the synthesis of several related analogs for the structureactivity relationship study. 11 Several PMHs were previously synthesized to establish the anticonvulsant structure-activity relationship of this class.…”

Section: Introductionmentioning

confidence: 99%

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. a b s t r a c tThe Red Sea sponge Hemimycale arabica afforded the known (Z)-5-(4-hydroxybenzylidene)-hydantoin (1), (R)-5-(4-hydroxybenzyl)hydantoin (2), and (Z)-5-((6-bromo-1H-indol-3-yl)methylene)-hydantoin (3). The natural phenylmethylene hydantoin (PMH) 1 and the synthetic (Z)-5-(4-(ethylthio)benzylidene)-hydantoin (4) showed potent in vitro anti-growth and anti-invasive properties against PC-3M prostate cancer cells in MTT and spheroid disaggregation assays. PMHs 1 and 4 also showed significant anti-invasive activities in orthotopic xenograft and transgenic mice models. To study the effect of electronic and lipophilic parameters on the activity, a wide array of several substituted aldehydes possessing electron-withdrawing (+r), lipophilic (+p), electron-donating (Àr), and less lipophilic substituents (Àp) were used to synthesize several PMHs. Few des-phenylmethylenehydantoins and 2-thiohydanoins were also synthesized and the anti-invasive activities of all compounds were evaluated. Comparative molecular field analysis (CoMFA) was then used to study the 3D QSAR. Predictive 3D QSAR model with conventional r 2 and cross validated coefficient (q 2 ) values up to 0.910 and 0.651 were established. In conclusion, PMH is a novel antimetastatic lead class with potential to control metastatic prostate cancer.

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Section: Introductionmentioning

confidence: 99%

Discovery, design, and synthesis of anti-metastatic lead phenylmethylene hydantoins inspired by marine natural products

Mudit

Khanfar

Anbalagan

et al. 2009

Bioorganic & Medicinal Chemistry

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“…Therefore, there is certainly room to explore further the plant kingdom, more deeply and perhaps differently compared to what has been done so far, using novel targets and novel methodological approaches. Despite these difficulties, several authors maintain the idea that plant NP can return to the forefront of anticancer pharmacology [43]. In the past, traditional screening approaches have allowed a rich harvest of "low hanging fruits".…”

Section: Microorganisms: the Main Supplier Of Anticancer Structurallymentioning

confidence: 99%

Ready for a comeback of natural products in oncology

Bailly

2009

Biochemical Pharmacology

101

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(186 words)Since the late 1990s and the rapid expansion of monoclonal antibodies and synthetic protein kinase inhibitors in oncology, anticancer natural products fell out of fashion with the pharmaceutical industry. But in 2007 with the approval of three new drugs derived from natural products, the emergence of promising antitumor compounds from microorganisms (e.g. alvespimycin, salinosporamide) and the growing importance of new formulations of known natural product-derived drugs (nanoparticle formulations, oral forms), we are witnessing a new wave for natural products in oncology. The recent approval of the microtubule-targeted epothilone derivative ixabepilone (Ixempra ® ), the DNA-alkylating marine alkaloid trabectedin (Yondelis ® ) and the inhibitor of mTOR protein kinase temsirolimus (Torisel ® ) is emblematic of the evolution of the field which combines the long established finding of conventional cytotoxic agents and the emergence of molecularly targeted therapeutics. These three examples also illustrate the increasing importance of microbial sources for the discovery of medically useful natural products. The contribution of innovative biological targets is also highlighted here, with references to proteasome inhibitors and novel approaches such as manipulation of mRNA splicing. Altogether, these observations plead for the return of natural products in oncology.

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“…As most productive sources, medicinal plants provide a large number of molecules that could be screened to find potential lead compounds for drug discovery [1,2]. Nowadays, the main concerns for the phytotherapeutics are the efficacy, safety and quality of phytomedicines [3,4].…”

Section: Introductionmentioning

confidence: 99%