For Publishers
DiscoveryMetadataPeer reviewHostingPublishing
For Researchers
JoinPublishReviewCollect
Register
Blog
About
Search
Advanced search
My ScienceOpen
Search
For Publishers
For Researchers
Blog
About
3
views
61
references
 Top references
cited by
5
    
0 reviews
 Review
0
comments
 Comment
0
recommends
+1 Recommend
0 collections
    0
    shares
      2,879
      similar
       All similar
      • Record: found
      • Abstract: not found
      • Article: not found

      Synthetic and Biological Studies of Sesquiterpene Polygodial: Activity of 9-Epipolygodial against Drug-Resistant Cancer Cells

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          <p class="first" id="P1">Polygodial, a terpenenoid dialdehyde isolated from <i>Polygonum hydropiper</i> L., is a known TRPV1 agonist. In this investigation a series of polygodial analogues were prepared and investigated for TRPV1 agonistic and anticancer activities. These experiments led to the identification of 9-epipolygodial, possessing antiproliferative potency significantly exceeding that of polygodial. Epipolygodial maintained potency against apoptosis-resistant cancer cells as well as those displaying the MDR phenotype. In addition, a chemical feasibility for the previously proposed mechanism of action of polygodial, involving the Paal-Knorr pyrrole formation with a lysine residue on the target protein, was demonstrated through the synthesis of a stable polygodial pyrrole derivative. These studies reveal rich chemical and biological properties associated with polygodial and its direct derivatives. They should inspire further work in this area aimed at the development of new pharmacological agents or exploration of novel mechanisms of covalent modification of biological molecules with natural products. </p><p id="P2"> <div class="figure-container so-text-align-c"> <img alt="" class="figure" src="/document_file/30a50472-ae76-49fc-a3d0-451e97c1e159/PubMedCentral/image/nihms-741864-f0001.jpg"/> </div> </p>

          Related collections

          Most cited references61

          • Record: found
          • Abstract: found
          • Article: not found

          TRPV1 structures in distinct conformations reveal mechanisms of activation

          Erhu Cao, Maofu Liao, Yifan Cheng … (2013)
          TRP channels are polymodal signal detectors that respond to a wide range of physical and chemical stimuli. Elucidating how these channels integrate and convert physiological signals into channel opening is essential to understanding how they regulate cell excitability under normal and pathophysiological conditions. Here we exploit pharmacological probes (a peptide toxin and small vanilloid agonists) to determine structures of two activated states of the capsaicin receptor, TRPV1. A domain (S1-S4) that moves during activation of voltage-gated channels remains stationary in TRPV1, highlighting differences in gating mechanisms for these structurally related channel superfamilies. TRPV1 opening is associated with major structural rearrangements in the outer pore, including the pore helix and selectivity filter, as well as pronounced dilation of a hydrophobic constriction at the lower gate, suggesting a dual gating mechanism. Allosteric coupling between upper and lower gates may account for rich physiologic modulation exhibited by TRPV1 and other TRP channels.
          Article 0 comments Cited 377 times – based on 0 reviews     Review now
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            The vanilloid receptor: a molecular gateway to the pain pathway.

            M. J. Caterina, D Julius (2001)
            The detection of painful stimuli occurs primarily at the peripheral terminals of specialized sensory neurons called nociceptors. These small-diameter neurons transduce signals of a chemical, mechanical, or thermal nature into action potentials and transmit this information to the central nervous system, ultimately eliciting a perception of pain or discomfort. Little is known about the proteins that detect noxious stimuli, especially those of a physical nature. Here we review recent advances in the molecular characterization of the capsaicin (vanilloid) receptor, an excitatory ion channel expressed by nociceptors, which contributes to the detection and integration of pain-producing chemical and thermal stimuli. The analysis of vanilloid receptor gene knockout mice confirms the involvement of this channel in pain sensation, as well as in hypersensitivity to noxious stimuli following tissue injury. At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain.
            Article 0 comments Cited 267 times – based on 0 reviews     Review now
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Irreversible inhibitors of the EGF receptor may circumvent acquired resistance to gefitinib.

              Joseph W Lynch, K Isselbacher, P. Harris … (2005)
              Non-small cell lung cancers (NSCLCs) with activating mutations in the kinase domain of the epidermal growth factor receptor (EGFR) demonstrate dramatic, but transient, responses to the reversible tyrosine kinase inhibitors gefitinib (Iressa) and erlotinib (Tarceva). Some recurrent tumors have a common secondary mutation in the EGFR kinase domain, T790M, conferring drug resistance, but in other cases the mechanism underlying acquired resistance is unknown. In studying multiple sites of recurrent NSCLCs, we detected T790M in only a small percentage of tumor cells. To identify additional mechanisms of acquired resistance to gefitinib, we used NSCLC cells harboring an activating EGFR mutation to generate multiple resistant clones in vitro. These drug-resistant cells demonstrate continued dependence on EGFR and ERBB2 signaling for their viability and have not acquired secondary EGFR mutations. However, they display increased internalization of ligand-activated EGFR, consistent with altered receptor trafficking. Although gefitinib-resistant clones are cross-resistant to related anilinoquinazolines, they demonstrate sensitivity to a class of irreversible inhibitors of EGFR. These inhibitors also show effective inhibition of signaling by T790M-mutant EGFR and killing of NSCLC cells with the T790M mutation. Both mechanisms of gefitinib resistance are therefore circumvented by irreversible tyrosine kinase inhibitors. Our findings suggest that one of these, HKI-272, may prove highly effective in the treatment of EGFR-mutant NSCLCs, including tumors that have become resistant to gefitinib or erlotinib.
              Article 0 comments Cited 156 times – based on 0 reviews     Review now
                Bookmark
                All references

                Author and article information

                Journal
                Title: ChemMedChem
                Abbreviated Title: ChemMedChem
                Publisher: Wiley
                ISSN: 18607179
                Publication date Created: December 2015
                Publication date (Print): December 2015
                Publication date (Electronic): October 05 2015
                Volume: 10
                Issue: 12
                Pages: 2014-2026
                Affiliations
                [1 ]Department of Chemistry and Biochemistry; Texas State University; San Marcos TX 78666 USA
                [2 ]Laboratoire de Cancérologie et de Toxicologie Expérimentale; Faculté de Pharmacie; Université Libre de Bruxelles; 1050 Brussels Belgium
                [3 ]Laboratoire de Physiologie Cellulaire et Moléculaire; Faculté des Sciences; Université de Picardie Jules Verne; 80000 Amiens France
                [4 ]Neurosurgical Research; University Clinics Munich; Marchioninistr. 15 81377 Munich Germany
                [5 ]Departments of Chemistry and Biology; New Mexico Institute of Mining and Technology; 801 Leroy Place Socorro NM 87801 USA
                [6 ]Center of Innovation and Preclinical Studies; Av. Luiz Boiteux Piazza 1302, Cachoeira do Bom Jesus Florianópolis SC 88056-000 Brazil
                [7 ]Department of Pharmacology; Federal University of Santa Catarina; Florianópolis SC Brazil
                [8 ]Department of Comprehensive Dentistry; Cancer Therapy and Research Center; University of Texas Health Science Center at San Antonio; San Antonio TX 78229 USA
                [9 ]Department of Pharmacology; University of Texas Health Science Center at San Antonio; San Antonio TX 78229 USA
                [10 ]Department of Biomedical Sciences, College of Medicine; University of Illinois; 1601 Parkview Ave. Rockford IL 61107 USA
                [11 ]Dipartimento di Scienze Chimiche; Università di Napoli Federico II; Complesso Universitario Monte Sant'Angelo; Via Cintia 4 80126 Napoli Italy
                [12 ]Departamento de Biologia Celular e Molecular; Instituto de Biologia; Universidade Federal Fluminense; Outeiro de São João Batista, s/n Campus do Valonguinho Centro-Niterói RJ 24020-140 Brazil
                [13 ]Department of Chemistry and Polymer Science; Stellenbosch University; Stellenbosch Private Bag X1, Matieland 7602 South Africa
                Article
                DOI: 10.1002/cmdc.201500360
                PMC ID: 4831215
                PubMed ID: 26434977
                SO-VID: 0b66ffa5-cdc2-4584-92d6-3cb6064d1466
                Copyright © © 2015
                License:

                http://doi.wiley.com/10.1002/tdm_license_1.1

                History

                Data availability:

                Comments

                Comment on this article

                scite_

                Similar content2,879

                See all similar

                Cited by5

                See all cited by

                Most referenced authors1,028

                See all reference authors