A degradation study of a series of chloromethyl and diazomethyl ketone anti-leukemic agents

Drug Development and Industrial Pharmacy
Ann T KotchevarF M Uckun

Abstract

The chemical stability of a novel cysteine chloromethyl ketone derivative (HI-131) with anti-leukemic activity has been investigated in a microemulsion formulation. HI-131 degrades to two major products, most likely by undergoing oxidation and further reaction with another HI-131 molecule to form higher molecular weight oligomers of the original compound. The degradation kinetics of HI-131 have been studied as a function of pH, buffer composition, ionic strength, and temperature. Degradation follows pseudo-first-order kinetics and the temperature effect obeys the Arrhenius equation. The pH-rate profile demonstrates HI-131 is most stable at lower pH values, although there is no significant influence of ionic strength and buffer ions on the degradation rate. The chemical stability of a homologous series of chloromethyl and diazomethyl ketone derivatives of HI-131 has also been investigated in microemulsion. The relationship between the chain length of the derivatives and the stability is presented. Changing the chloro group to a bromo group resulted in an increase in degradation rate. Alterations to the group on the nitrogen were also investigated. The changes to the stability are discussed in terms of their mechanistic implicati...Continue Reading

References

Mar 31, 2000·Bioorganic & Medicinal Chemistry Letters·D A PerreyF M Uckun

❮ Previous
Next ❯

Citations

Jan 21, 2021·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Gloria CastellanoFrancisco Torrens

❮ 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.