Establishing tentative cut-off values for disk diffusion method for <i>Pasteurella multocida</i> and <i>Mannheimia haemolytica</i> from livestock animals in Japan

Article

Author: KUMAKAWA, Mio ; HOSOI, Yuta ; SEKIGUCHI, Hideo ; MATSUDA, Mari ; AKAMA, Ryoko ; HIRAOKA, Yukari ; HARADA, Saki ; KAWANISHI, Michiko

Although the disk diffusion method is a useful and widely utilized antimicrobial susceptibility testing method in clinical veterinary practice, the available clinical breakpoints (CBPs) for the combination of bacterial species and antimicrobials are still limited. This study aimed to establish tentative cut-off values by analyzing the relationship between minimum inhibitory concentration and the inhibition zone diameter of the disk diffusion method for Pasteurella multocida and Mannheimia haemolytica, collected by the Japanese Veterinary Antimicrobial Resistance Monitoring system (JVARM), for the antimicrobial agents approved in Japan for the treatment of respiratory diseases in cattle and swine. Among the antimicrobial agents without CBPs for the disk diffusion method in the Clinical and Laboratory Standards Institute (CLSI), we were able to determine the tentative cut-off values of ampicillin (ABPC, S ≥25 mm, R ≤24 mm in swine), dihydrostreptomycin (DSM, S ≥8 mm in cattle, S ≥12 mm in swine), kanamycin (KM, S ≥16 mm in cattle, S ≥17 mm in swine), tetracycline (TC, S ≥21 mm, R ≤20 mm in cattle) and tiamulin (TML, S ≥13 mm in swine) for P. multocida, and CEZ (S ≥23 mm), DSM (S ≥10 mm), KM (S ≥18 mm) and TC (S ≥23 mm, R ≤20 mm) for M. haemolytica. These results should encourage the practical use of antimicrobial susceptibility testing in the clinical field and contribute to furthering prudent use of antimicrobial agents.

01 Dec 2024·Bioorganic Chemistry

A comprehensive review of synthetic strategies and SAR studies for the discovery of PfDHODH inhibitors as antimalarial agents. Part 2: Non-DSM compounds

Review

Author: Vyas, Vivek K ; Lolli, Marco L. ; Sharma, Manmohan ; Lolli, Marco L ; Vyas, Vivek K.

Malaria remains a severe global health concern, with 249 million cases reported in 2022, according to the World Health Organization (WHO) [1]. PfDHODH is an essential enzyme in malaria parasites that helps to synthesize certain building blocks for their growth and development. It has been confirmed that targeting Plasmodium falciparum dihydroorotate dehydrogenase (PfDHODH) enzyme could lead to new and effective antimalarial drugs. Inhibitors of PfDHODH have shown potential for slowing down parasite growth during both the blood and liver stages. Over the last two decades, many species selective PfDHODH inhibitors have been designed, including DSM compounds and other non-DSM compounds. In the first chapter [2] of this review, we have reviewed all synthetic schemes and structure-activity relationship (SAR) studies of DSM compounds. In this second chapter, we have compiled all the other non-DSM PfDHODH inhibitors based on dihydrothiophenones, thiazoles, hydroxyazoles, and N-alkyl-thiophene-2-carboxamides. The review not only offers an insightful overview of the synthetic methods employed but also explores into alternative routes and innovative strategies involving different catalysts and chemical reagents. A critical aspect covered in the review is the SAR studies, which provide a comprehensive understanding of how structural modifications impact the efficacy of PfDHODH inhibitors and challenges related to the discovery of PfDHODH inhibitors. This information is invaluable for scientists engaged in the development of new antimalarial drugs, offering insights into the most promising scaffolds and their synthetic techniques.

01 Dec 2024·Asian Pacific Journal of Cancer Prevention

Hesperidin and Diosmin Increased Cytotoxic Activity Cisplatin on Hepatocellular Carcinoma and Protect Kidney Cells Senescence

Article

Author: Rumiyati, Rumiyati- ; Jenie, Riris Istighfari ; Artanti, Anif Nur ; Meiyanto, Edy

OBJECTIVECisplatin (Cisp) is a chemotherapy drug for treating liver cancer. Hesperidin (HSD), a flavanone, is known for its anticancer, and anti-inflammatory properties. Diosmin (DSM), a flavone glycoside, is known for its anti-oxidant effect. This research investigated the synergism cytotoxic effect and senescence selectivity effect of HSD or DSM co-treatment with Cisp on HepG2 cells and Vero cells.METHODSThe cytotoxicity and cell viability of HSD or DSM combined with Cisp on HepG2 and Vero cells were assessed using the MTT assay with IC50 parameters, selectivity index (SI), and Combination Index (CI), while the antiproliferative profile was determined by colony-forming assay. Cellular senescence on HepG2 and Vero cell lines was determined using senescence-associated β-galactosidase (SA-β-gal) staining. Furthermore, the impact of apoptosis was evaluated using flowcitometry.RESULTIn the MTT assay, HSD, DSM, and cisplatin exhibited cytotoxic effects on HepG2 cells, with IC50 values of 321 µM, 148 µM, and 5 µM, respectively. Co-treatment with HSD and DSM with cisplatin enhanced cell sensitivity, resulting in a combination index of < 1. HSD and DSM exhibited minimal cytotoxicity against Vero cells, with IC50 values exceeding 500 µM. Both HSD and DSM reduced cellular senescence in Vero cells caused by cisplatin exposure. These findings suggest that co-treatment with HSD and DSM alongside cisplatin can synergistically lessen the viability of HepG2 cells. The Annexin V-FITC/PI apoptosis assay also showed more cells undergoing apoptosis in the co-treatment group. Both co-treatment HSD and DSM with Cisp independently induced the senescence of HepG2 cells and reduced the cellular senescence of normal kidney cells.CONCLUSIONConsequently, both HSD and DSM show potential for development as co-treatment agents in combination with Cisp for hepatocellular carcinoma, and they may also be useful for reducing senescence in normal kidney cells.

100 Deals associated with Disodium malonate

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Reperfusion Injury	Preclinical	Australia	South Australian Health & Medical Research Institute Ltd.	30 Jan 2025
Reperfusion Injury	Preclinical	Australia	University of Adelaide	30 Jan 2025

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

Disodium malonate

Overview

Basic Info

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation