The culture broth of endophytic Streptomyces sp. AB100, isolated from the shoots of medicinal plant Atropa belladonna (L.) was investigated for the presence of antibacterial compounds. After initial testing followed by bioactivity-guided fractionation, six new piperazic acid (PA)-containing congeners of two known peptides, JBIR-39 and JBIR-40, were identified by HR-MS/MS and NMR analyses. Only the dehydroxylated hexapeptidic derivatives with unusual incorporation of four PA moieties exhibited weak antibacterial activity against Gram-positive test organism Bacillus subtilis. A 16S rDNA-based phylogenetic tree of known Streptomyces spp. producing PA-containing hexapeptides isolated from different habitats and endophyte Streptomyces AB100 showed considerable diversity, suggesting that these metabolites may play an important environmental role beyond their antibacterial activity.

01 Mar 1991·Biochemical PharmacologyQ2 · MEDICINE

Comparative chemical and biological studies of four prototype phosphoraziridine antineoplastic agents

Q2 · MEDICINE

Article

Author: Joseph A. Dunn ; Thomas J. Bardos

The chemical alkylating activities of four prototype phosphoraziridine antineoplastic agents were compared with their biological effects on V-79 Chinese hamster lung fibroblasts. It was found that the chemical reactivity patterns correlate well with all of the biological parameters examined in this study, i.e. cytotoxicity, DNA synthesis, and production of alkali labile strand breaks. Specifically, the 2,2-dimethylaziridine derivatives (AB-132 and AB-163) showed higher initial activities reaching a plateau after a short reaction time in all of the systems used in this study while the unsubstituted aziridine derivatives (AB-100 and D-63) reacted more slowly but continued to exert their action in a linear fashion to produce greater overall effects. These findings are consistent with the conclusion that the difference between the time-dependent biological activities of these drugs closely follows the different chemical mechanisms of their alkylating reactions (SN1 vs SN2). The more rapid action and subsequent hydrolytic inactivation of the 2,2-dimethylphosphoraziridines as effective alkylators could be the basis of their lower hemopoietic toxicity compared to conventional alkylating agents including their own C-unsubstituted aziridine analogs. The much more rapid action of the 2,2-dimethylphosphoraziridines on DNA inside the cell may have some bearing on their radiation potentiating activity, but this aspect and the cholinesterase inhibitory activity of these agents (which may depend on phosphorylation) were not investigated in the present study.

01 Aug 1970·Journal of Pharmaceutical SciencesQ3 · MEDICINE

Mechanisms of Reactions of Ring-Substituted Bis(1-aziridinyl) phosphinyl Urethan Antineoplastic Agents

Q3 · MEDICINE

Article

Author: Z.F. Chmielewicz ; C.K. Navada ; T.J. Bardos

Bis(trans-2,3-dimethylaziridinyl)phosphinyl urethane (I) was synthesized and compared with the corresponding cis-2,3-dimethyl derivative (II).The comparative alkylating activities and rates of hydrolysis of these two stereoisomeric aziridine derivatives, I and II, were determined and compared with corresponding data for the monomethyl derivative (III) and two other clinically tested members of this series of antineoplastic agents (dual antagonists), AB-100 (IV) and AB-132 (V).The structures of the final hydrolysis products of I, II, and III were determined and confirmed by direct synthesis.The results indicate that the mechanisms of hydrolysis of I, II, and III (as that of the unsubstituted aziridine derivative IV) are essentially SN2, in contrast to the much faster hydrolysis of the 2,2-dimethyl-aziridine analog (V) which involves a carbonium-ion mechanism.These studies give further support to the hypothesis that the unique pharmacol. properties of V, as compared to other members of this series, may be related to the unique chem. properties of the 2,2-dimethylaziridine moieties.

100 Deals associated with AB-100

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Herpes Simplex	Discovery	ES	Applied Research Using Omic Sciences SL	12 Oct 2022

Clinical Result

Indication

Phase

Evaluation

View All Results

Translational Medicine

Boost your research with our translational medicine data.

view full example data

Deal

Boost your decision using our deal data.

view full example data

Core Patent

Boost your research with our Core Patent data.

view full example data

Clinical Trial

Identify the latest clinical trials across global registries.

view full example data

Approval

Accelerate your research with the latest regulatory approval information.

view full example data

Regulation

Understand key drug designations in just a few clicks with Synapse.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis


No Data

AB-100

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation