A pharmacophore modeling approach to design new taxol® mimics: towards the synthesis of potential anticancer and MDR-reversing agent

Renzulli, Michela L.; Rocheblave, Luc; Avramova, Stanislava I.; Galletti, Elena; Castagnolo, Daniele; Maccari, Laura; Forli, Stefano; Manetti, Fabrizio; Corelli, Federico; Botta, Maurizio

doi:10.3998/ark.5550190.0007.812

Cited by 4 publications

(1 citation statement)

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“…Besides, this molecule also binds to Bcl-2 protein, thus inducing apoptosis (Sinha et al, 2011). Whilst vincristine, belonging to the group of vinca alkaloids, exhibits antimitotic activity by inhibiting microtubule assembly (Renzulli et al, 2006).…”

Section: Bioinformatics-genomic Molecular Target-biomarkermentioning

confidence: 99%

Translational Research in Cancer Drug Development

Meiyanto

Hermawan

Anindyajati

2011

Indones J Cancer Chemoprevent

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The development of cancer treatment were initiated by the existence of human’s effort to treat by applying certain materials which is mostly part(s) or extracts of plants, which are now adapted as traditional herbal medicine. The discovery of new drugs was based on intuition and empirical evidence. Thus, high luck factor was involved in a successful treatment with unguaranteed reproducibility. One example of drug being developed through conventional drug development is Taxol. Taxol is an extremely complex natural product and requires a bunch of hard work with high level of serendipity to be discovered as antitumor agent. Recently, rapid development in human biology and technology allow a change in drug discovery strategy by minimizing the luck factor. Targeted therapy has been a very promising strategy of drug development research, especially in cancer treatment. Although cancer has been known as a disease with very complex cellular and histo-pathophysiology, the abundance of studies on proteins, such as receptors and hormones, as the hallmarks of cancer allows us to explore carcinogenesis suppression further based on molecular targeted therapy. Kinases, one type of protein involved in signal transduction regulating cell growth and differentiation, could be the proteins that are proposed to be inhibited in suppressing tumor growth. An interesting example of the drug being discovered based on molecular modeling is the discovery of lapatinib as anti- cancer with specific target on HER-2 and EGFR to overcome the resistance of cancer to Herceptin caused by elevated level of EGFR expression.Keywords : targeted therapy, cancer, translational drug development

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Section: Bioinformatics-genomic Molecular Target-biomarkermentioning

confidence: 99%

Translational Research in Cancer Drug Development

Meiyanto

Hermawan

Anindyajati

2011

Indones J Cancer Chemoprevent

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Olefin Ring‐Closing Metathesis

Yet

2016

Organic Reactions

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The olefin ring‐closing metathesis reaction catalyzed by ruthenium and molybdenum complexes has been employed in the syntheses of carbocycles, heterocycles, supramolecular compounds, and in tandem metathesis reactions. Chiral ruthenium and molybdenum catalysts have provided high enantiomeric and diastereomeric excesses in ring‐closing metathesis reactions. Many of the unsuccessful medium‐ and large‐sized ring formations which were unsuccessful by traditional methods, such as the intramolecular Wittig, Horner–Wadsworth–Emmons, and Julia–Kocienski reactions, can now be formed by olefin ring‐closing metathesis reactions. Ring‐closing metathesis has been a key step and sometimes the only successful method for the synthesis of numerous natural products and drug discovery targets. The objective of this chapter is to provide an updated, comprehensive coverage of the literature of the olefin ring‐closing metathesis reaction and related processes. Key mechanistic points are summarized.

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