Synthesis and antitumor evaluation of nitrovinyl biphenyls: anticancer agents based on allocolchicines

ChemMedChem
Nishant JainB Sreedhar

Abstract

A new class of nitrovinyl biphenyl compounds based on the structures of colchicines and allocolchicines were designed, synthesized, and shown to inhibit tubulin polymerization and cause mitotic arrest. A majority of these compounds were found to possess potent anticancer properties, with IC(50) values in the range of 0.05-7 μM, and are equally potent with colchicine in HeLa and MCF-7 cells. Compounds 14 e and 14 f inhibited tubulin assembly by more than 60 %, and flow cytometry studies indicated growth arrest of cells in the G(2)/M phase of the cell cycle in a concentration-dependent manner. Treatment of cells with 14 f resulted in upregulation of cyclin B1 and aurora kinase B mRNA levels, corresponding to growth arrest in the G(2)/M phase of the cell cycle as the mode of action.

References

Mar 1, 1996·Medicinal Research Reviews·E Hamel
Jun 1, 1997·Molecular Biology of the Cell·R J VasquezL Cassimeris
Jul 17, 1998·Medicinal Research Reviews·A JordanA T McGown
Jan 27, 2000·Cell·D Hanahan, R A Weinberg
Mar 25, 2000·Bioorganic & Medicinal Chemistry·René BrechtSylviane Thoret
Apr 16, 2003·Molecular Pharmacology·Joo Hee KimIn Kwon Chung
Mar 17, 2004·Trends in Pharmacological Sciences·Anthony H FutermanAri Zimran
Apr 2, 2004·Nature Reviews. Cancer·Mary Ann Jordan, Leslie Wilson
Jun 24, 2004·Angewandte Chemie·Timm Graening, Hans-Günther Schmalz
Oct 16, 2004·Cell Cycle·Alwin KrämerJiri Bartek
Nov 19, 2004·Nature·Charles Sawyers
Dec 8, 2004·Mini Reviews in Medicinal Chemistry·Mohd N Islam, Magdy N Iskander
Jul 1, 2005·Organic Letters·Mélissa Leblanc, Keith Fagnou
Mar 14, 2007·Anti-cancer Agents in Medicinal Chemistry·Alex KiselyovAlexandre V Ivachtchenko
Mar 14, 2007·Chemistry : a European Journal·Agnès JoncourOlivier Baudoin
Apr 28, 2007·Medicinal Research Reviews·Bhabatarak BhattacharyyaMithu Banerjee
May 29, 2007·Chemical Research in Toxicology·Wan-Ping HuJeh-Jeng Wang
Nov 30, 2007·Organic Letters·Sinisa Djurdjevic, James R Green
Jan 19, 2008·Molecular Cancer Therapeutics·Kelly HuberStewart Martin
Feb 22, 2008·Current Medicinal Chemistry·A Petrelli, S Giordano
Jun 10, 2008·Current Medicinal Chemistry·André Schrattenholz, Vukić Soskić
Aug 1, 2008·Current Clinical Pharmacology·Isa E L M Kuppens
Dec 27, 2008·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Cornelis J Van der Schyf, Werner J Geldenhuys
Jun 13, 2009·Current Pharmaceutical Design·Peng Zhan, Xinyong Liu
Jun 19, 2009·Nature Reviews. Cancer·Ann M Bode, Zigang Dong
Jun 18, 2010·European Journal of Medicinal Chemistry·Ahmed KamalShasi V Kalivendi

Citations

Jan 15, 2013·European Journal of Medicinal Chemistry·A Suresh KumarB Sreedhar
Jan 5, 2016·Bioorganic & Medicinal Chemistry Letters·Sebastian AnushaKanchugarakoppal S Rangappa
Mar 17, 2016·The Journal of Organic Chemistry·Atul Ashok More, Chepuri V Ramana
Apr 24, 2016·Chemistry : a European Journal·David SchweinfurthFrançois Diederich
Dec 3, 2014·Bioorganic & Medicinal Chemistry Letters·Naresh Kumar ManchukondaSrinivas Kantevari
Dec 8, 2014·Journal of Computer-aided Molecular Design·Seneha SantoshiPradeep K Naik
Jul 29, 2016·ChemMedChem·P S SrikanthAhmed Kamal
Apr 24, 2019·Journal of Asian Natural Products Research·Uppuluri Venkata MallavadhaniNishanth Jain

Related Concepts

Diphenyl, 14C-labeled
Allocolchicine
AURKB protein, human
Antineoplastic Agents
Biphenyl Compounds
Cell Division Phases
Colchicine, (R)-Isomer
Dye Exclusion Assays, Antitumor
Malignant Neoplasms
Delta-Tubulin

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Alzheimer's Disease: MS4A

Variants within the membrane-spanning 4-domains subfamily A (MS4A) gene cluster have recently been implicated in Alzheimer's disease in genome-wide association studies. Here is the latest research on Alzheimer's disease and MS4A.

Pediculosis pubis

Pediculosis pubis is a disease caused by a parasitic insect known as Pthirus pubis, which infests human pubic hair, as well as other areas with hair including eye lashes. Here is the latest research.

Rh Isoimmunization

Rh isoimmunization is a potentially preventable condition that occasionally is associated with significant perinatal morbidity or mortality. Discover the latest research on Rh Isoimmunization here.

Genetic Screens in iPSC-derived Brain Cells

Genetic screening is a critical tool that can be employed to define and understand gene function and interaction. This feed focuses on genetic screens conducted using induced pluripotent stem cell (iPSC)-derived brain cells. It also follows CRISPR-Cas9 approaches to generating genetic mutants as a means of understanding the effect of genetics on phenotype.

Enzyme Evolution

This feed focuses on molecular models of enzyme evolution and new approaches (such as adaptive laboratory evolution) to metabolic engineering of microorganisms. Here is the latest research.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Pharmacology of Proteinopathies

This feed focuses on the pharmacology of proteinopathies - diseases in which proteins abnormally aggregate (i.e. Alzheimer’s, Parkinson’s, etc.). Discover the latest research in this field with this feed.

Alignment-free Sequence Analysis Tools

Alignment-free sequence analyses have been applied to problems ranging from whole-genome phylogeny to the classification of protein families, identification of horizontally transferred genes, and detection of recombined sequences. Here is the latest research.