Cytotoxic esters of 1,1-bis-(4-hydroxyphenyl)-2-phenyl-but-1-ene with selective antitumor activity against estrogen receptor-containing mammary tumors

Journal of Cancer Research and Clinical Oncology
M L Schuderer, M R Schneider

Abstract

Both hydroxy groups of 1,1-bis-(4-hydroxyphenyl)-2-phenyl-but-1-ene (1) were esterified with the beta-chloropropionate (2), beta-bromopropionate (3) and acrylate functions (4). Linkage of these cytotoxic moieties reduced the estrogen receptor affinities of these compounds, especially in the case of the beta-haloesters only slightly compared with the affinity of the unsubstituted carrier molecule 1. The estrogenic potencies of the derivatives 2-4 and of 1 were nearly identical. The alkylating activities increased in the order 2, 3, and 4. Because of their alkylating activities, all cytotoxic esters showed an irreversible mode of binding to the estrogen receptor. In vitro, 3 in particular, exerted better growth inhibition of the hormone-dependent MCF-7 cell line than of the hormone-independent MDA cell line. In vivo, all cytotoxic derivatives caused almost complete inhibition of the growth of the hormone-dependent MXT M3.2 mouse mammary tumor, whereas growth of the hormone-independent MXT-Ovex tumor was much less inhibited. In all tumor models, the antitumor effect of the cytotoxic esters was better than that of the unsubstituted carrier. Therefore, the antitumor activity of these esters could be due not only to their improved ph...Continue Reading

References

Feb 1, 1979·Journal of Medicinal Chemistry·H Y LamC M Wong
Dec 15, 1976·International Journal of Cancer. Journal International Du Cancer·G LeclercqJ C Heuson
Dec 1, 1985·Journal of Medicinal Chemistry·M R SchneiderH Schönenberger
Jul 1, 1974·Journal of Pharmaceutical Sciences·K H LeeT A Geissman
Jan 1, 1983·Journal of Medicinal Chemistry·E von Angerer, J Prekajac
Aug 1, 1980·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·W D BloomerJ B Little
May 1, 1963·The Journal of Surgical Research·T J MCNAIRJ A DEPEYSTER
Mar 1, 1965·Journal of Medicinal Chemistry·T J BARDOSD J TRIGGLE

❮ Previous
Next ❯

Citations

Mar 10, 2007·Bioorganic & Medicinal Chemistry Letters·Isamu ShiinaYoshimune Hasome
Sep 1, 1990·Cancer Treatment Reviews·P J BednarskiH Schönenberger
Feb 1, 1989·European Journal of Cancer & Clinical Oncology·N KnebelE von Angerer

❮ Previous
Next ❯

Related Concepts

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.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

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.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.