In vitro and silico activity of piperlongumine against azole-susceptible/resistant Aspergillus fumigatus and terbinafine-susceptible/resistant Trichophyton species

Article

Author: Teymoori, Ali ; Hedayati, Mohammad Taghi ; Otaševi´c, Suzana ; Ebrahimi-Barough, Robab ; Haghani, Iman ; Sillanpää, Mika ; Hoseinnejad, Akbar ; Nosratabadi, Mohsen ; Azadeh, Hossein ; Abastabar, Mahdi ; Aghili, Seyed Reza ; Yahyazadeh, Zahra ; Badali, Hamid ; Shokohi, Tahereh ; Rashidi, Mohsen ; Otasevic, Suzana ; Hashemi, Seyedeh Mahdieh

In recent years, the widespread emergence of drug resistance in yeasts and filamentous fungi to existing antifungal armamentariums has become a severe threat to global health. There is also concern regarding increased rates of azole resistance in Aspergillus fumigatus and Terbinafine resistance in Trichophyton species. To overcome this concern of resistance to regular therapies, new antifungal drugs with novel and effective mechanisms are crucially needed. Herbal remedies may be promising strategies for the treatment of resistant infections. We aimed to investigate the in vitro and silico activity of piperlongumine against clinical azole susceptible/resistant A. fumigatus and terbinafine-susceptible/resistant Trichophyton species. In the current study, piperlongumine demonstrated potent antifungal activity, with minimum inhibitory concentrations (MICs) ranging from 0.016-4 μg/mL against Trichophyton isolates and 0.25-2 μg/mL for A. fumigatus isolates. Additionally, molecular docking studies indicated that piperlongumine has a strong binding affinity to the active sites of squalene epoxidase and sterol 14-alpha demethylase. However, further studies are warranted to correlate these findings with clinical outcomes and provide the basis for further investigations to pave the way for developing novel antifungal agents.

31 Dec 2024·Animal Cells and Systems

Piperlongumine regulates genes involved in the skin barrier in epidermal keratinocyte HaCaT cells

Article

Author: Kim, Wanil ; Kang, Deok Gyeong ; Lee, Kyung-Ha ; Kim, Do-Yeon ; Kim, Dae-Wook ; Do, Hwan-Kwon

Given that the skin is the largest tissue in the human body, performing external barrier functions with innate and adaptive immunity and undergoing substantial changes during aging, it is under investigation as a major target of various bioactive molecules. In the present study, we examined the biological activity of the senolytic piperlongumine by analyzing alterations in mRNA expression of notable skin genes using transformed aneuploid immortal epidermal keratinocytes, HaCaT cells. We observed that piperlongumine increased the mRNA expression of genes playing critical roles in skin barrier function. In addition, piperlongumine increased expression enzymes involved in the synthesis of ceramide, a major component of intercellular lipids. Furthermore, we measured the protein levels of various cytokines secreted by epidermal keratinocytes and found changes in the release of GRO-αβγ, CCL5, and MCP1. Additionally, we observed that piperlongumine treatment modulated the expression of keratinocyte-specific aging markers and influenced telomerase activity. Based on these findings, piperlongumine could regulate the physiological activity of epidermal keratinocytes to induce beneficial effects in human skin by regulating important skin-related genes.

01 Dec 2024·Biofilm

Pseudomonas aeruginosa quorum sensing and biofilm attenuation by a di-hydroxy derivative of piperlongumine (PL-18)

Article

Author: Schlichter Kadosh, Yael ; Gopas, Jacob ; Shagan, Marilou ; Ben-Zvi, Anat ; Mehlman, Tevie ; Saravana Kumar, Rajendran ; Brandis, Alexander ; Nisaa, Khairun ; Muthuraman, Subramani ; Karsagi Byron, Danit Lisa ; Kushmaro, Ariel

Bacterial communication, Quorum Sensing (QS), is a target against virulence and prevention of antibiotic-resistant infections. 16 derivatives of Piperlongumine (PL), an amide alkaloid from Piper longum L., were screened for QS inhibition. PL-18 had the best QSI activity. PL-18 inhibited the lasR-lasI, rhlR-rhlI, and pqs QS systems of Pseudomonas aeruginosa. PL-18 inhibited pyocyanin and rhamnolipids that are QS-controlled virulence elements. Iron is an essential element for pathogenicity, biofilm formation and resilience in harsh environments, its uptake was inhibited by PL-18. Pl-18 significantly reduced the biofilm biovolume including in established biofilms. PL-18-coated silicon tubes significantly inhibited biofilm formation. The transcriptome study of treated P. aeruginosa showed that PL-18 indeed reduced the expression of QS and iron homeostasis related genes, and up regulated sulfur metabolism related genes. Altogether, PL-18 inhibits QS, virulence, iron uptake, and biofilm formation. Thus, PL-18 should be further developed against bacterial infection, antibiotic resistance, and biofilm formation.

100 Deals associated with Piperlongumine

R&D Status

10 top R&D records.

to view more data

Indication	Highest Phase	Country/Location	Organization	Date
Glioma	Preclinical	US	TargTex SAStartup	19 Sep 2023
Breast Cancer	Preclinical	US	Harvard Medical School	13 Jul 2011

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

Piperlongumine

Overview

Basic Info

Structure

Related

R&D Status

Clinical Result

Translational Medicine

Deal

Core Patent

Clinical Trial

Approval

Regulation