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Article ; Conference proceedings: New formulations with royleanone derivatives from Plectranthus spp. to inhibit P-glycoprotein activity

Bangay, Gabrielle / Isca, Vera / Domínguez-Martín, Eva María / Santos, Daniel J.V.A. / Díaz-Lanza, Ana María / Saraiva, Lucília / Afonso, Carlos A.M. / Jovanovic, Mirna / Pesic, Milica / Ríjo, Patrícia

Planta Medica

2023 Volume 89, Issue 14

Event/congress	71st International Congress and Annual Meeting of the Society for Medicinal Plant and Natural Product Research (GA), Trinity College Dublin Ireland, 2023-07-02
Language	English
Publishing date	2023-11-01
Publisher	Georg Thieme Verlag KG
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	123545-x
ISSN	1439-0221 ; 0032-0943
ISSN (online)	1439-0221
ISSN	0032-0943
DOI	10.1055/s-0043-1774270
Database	Thieme publisher's database

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Book ; Online: Sounding Bodies

Pesic, Peter

Music and the Making of Biomedical Science

(The MIT Press)

2022

Series title	The MIT Press
Keywords	Wave mechanics (vibration & acoustics) ; History of medicine ; 20th century & contemporary classical music ; Wave mechanics (vibration and acoustics) ; History of music
Language	0\|e
Size	1 electronic resource (408 pages)
Publisher	The MIT Press
Publishing place	Cambridge
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT021620941
ISBN	9780262046350 ; 0262046350
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Potential of Natural-Based Anticancer Compounds for P-Glycoprotein Inhibition.

Dinić, Jelena / Podolski-Renić, Ana / Jeremić, Marko / Pešić, Milica

Current pharmaceutical design

2019 Volume 24, Issue 36, Page(s) 4334–4354

Abstract: ... transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming ... drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able ... natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or ...

Abstract	Medicinal value of natural products comes from symbiotic and competitive evolution in Earth's complex biosphere. Billions of years of co-evolutionary interactions among millions of species have produced a large repertoire of defense molecules effective in fighting bacteria, viral, and fungal pathogens. Each species contains millions of different and useful molecules and new research technologies enabled the screening of molecules and complex mixtures from diverse biological sources. Traditional use of plants and other species led to the discovery of many bioactive compounds with various properties. In the last four decades, a large number of them were evaluated for their potential to treat cancer. Penetration of drugs into the cancer cell is necessary for their lethal pharmacological effect through interaction with intracellular target molecules. Increased activity of membrane efflux pumps reduces the intracellular drug accumulation, thereby preventing drug-target interactions. The discovery of the efflux transporter P-glycoprotein (P-gp) in multidrug resistant (MDR) cancer cells prompted the efforts in overcoming drug resistance by P-gp inhibition. The search for nontoxic anticancer agents from natural sources able to overcome MDR has been imperative in the field of drug design and discovery. Herein, we review various natural compounds from diverse sources emphasizing their potential to inhibit P-gp activity and/or expression.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1/antagonists & inhibitors ; Animals ; Antineoplastic Agents/pharmacology ; Biological Products/pharmacology ; Drug Design ; Drug Discovery/methods ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Neoplasm/drug effects ; Humans ; Neoplasms/drug therapy ; Neoplasms/pathology
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Antineoplastic Agents ; Biological Products
Language	English
Publishing date	2019-01-15
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1304236-1
ISSN	1873-4286 ; 1381-6128
ISSN (online)	1873-4286
ISSN	1381-6128
DOI	10.2174/1381612825666190112164211
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Article: Molecular DNA barcoding of the water mite genus Protzia Persig, 1896 with a description of three new species and the unknown male of P. longiacetabulata (Acari, Hydrachnidia)

Pešić, Vladimir / Smit, Harry / Gülle, Pinar / Dabert, Miroslawa

Systematic and applied acarology. 2021 July 12, v. 26, no. 7

2021

Abstract: ... freshwater mites. Here, we provide COI barcodes for five species (Protzia rugosa, P. rotunda, P. halberti, P ... cabardinica, P. longiacetabulata) and use them for species delimitation analyses accompanied ... with morphological comparisons. As a result, we resurrected the species P. cabardinica (Sokolow, 1940). Based ...

Abstract	Species of the mite genus Protzia Piersig, 1896 are diverse and sometimes highly abundant freshwater mites. Here, we provide COI barcodes for five species (Protzia rugosa, P. rotunda, P. halberti, P. cabardinica, P. longiacetabulata) and use them for species delimitation analyses accompanied with morphological comparisons. As a result, we resurrected the species P. cabardinica (Sokolow, 1940). Based on morphology only, we describe three new species, P. kyrgyzicasp. nov. and P. tienshanensissp. nov., from Kyrgyzstan and P. iranicasp. nov. from southern Iran. Furthermore, we describe the male of P. longiacetabulata from Turkey, which was not known previously.
Keywords	Acari ; DNA barcoding ; acarology ; freshwater ; males ; new species ; water mites ; Iran ; Kyrgyzstan
Language	English
Dates of publication	2021-0712
Size	p. 1213-1228.
Publishing place	Systematic and Applied Acarology Society
Document type	Article
ZDB-ID	2027206-6
ISSN	2056-6069 ; 1362-1971
ISSN (online)	2056-6069
ISSN	1362-1971
DOI	10.11158/saa.26.7.3
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Royleanone Analogues from Plectranthus spp. Demonstrate P-gp Inhibition and PKC Modulation

Gabrielle Bangay / Vera M. S. Isca / Daniel J. V. A. Dos Santos / Ricardo J. Ferreira / Salvatore Princiotto / Mirna Jovanovic / Milica Pesic / Patricia Rijo

Medical Sciences Forum, Vol 14, Iss 144, p

2022 Volume 144

Abstract: ... of membrane transport proteins, such as P-glycoprotein (P-gp), or the selective modulation of protein kinases C (PKC) isoforms ... docking simulations, 10 semi-synthetic derivatives of Roy that displayed strong P-gp interactions ... cells, compared to normal lung fibroblasts MRC5. Moreover, they showed a reduction in P-gp activity ...

Abstract	The number of multidrug resistant (MDR) cancer cases across the globe is continuing to rise, such that the search for novel anti-cancer therapeutics is paramount. For instance, the overexpression of membrane transport proteins, such as P-glycoprotein (P-gp), or the selective modulation of protein kinases C (PKC) isoforms continues to be a major impediment to effective therapy. Known for their medicinal properties, species from Plectranthus have been reported to have cytotoxicity against various cancer cell lines due to diterpenes, such as 7α-acetoxy-6β-hydroxyroyleanone ( Roy ) and 6,7-dehydroroyleanone ( DeRoy ). Based on molecular docking simulations, 10 semi-synthetic derivatives of Roy that displayed strong P-gp interactions in silico were prepared. The antitumoral activity was evaluated in resistant human cancer cell lines NCI-H460/R and DLD1-TxR, showing three derivatives having the most prominent selectivity towards cancer cells, compared to normal lung fibroblasts MRC5. Moreover, they showed a reduction in P-gp activity in Rho123 accumulation and indicated P-gp inhibition in the DOX accumulation assay using the same resistant cell lines. Overall, it was demonstrated that three abietane diterpenoids induced P-gp inhibition in MDR cancer cell lines. As regards the PKC activity, further analogues were tested as PKC (α, βI, δ, ε and ζ) modulators; one benzoylated derivative showed the ability to selectively activate PKC-δ, while the natural compound DeRoy displayed improved PKC activity, compared with the positive control, in all tested isoforms. Further investigations are ongoing to prepare analogues of other biologically active diterpenoids to obtain potential hits as P-gp and PKC modulators.
Keywords	royleanones ; diterpenes ; P-gp ; PKC ; analogues ; cancer ; Medicine ; R
Subject code	616
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The gyrase inhibitor albicidin consists of p-aminobenzoic acids and cyanoalanine.

Cociancich, Stéphane / Pesic, Alexander / Petras, Daniel / Uhlmann, Stefanie / Kretz, Julian / Schubert, Vivien / Vieweg, Laura / Duplan, Sandrine / Marguerettaz, Mélanie / Noëll, Julie / Pieretti, Isabelle / Hügelland, Manuela / Kemper, Sebastian / Mainz, Andi / Rott, Philippe / Royer, Monique / Süssmuth, Roderich D

Nature chemical biology

2015 Volume 11, Issue 3, Page(s) 195–197

Abstract: ... polyaromatic oligopeptide mainly composed of p-aminobenzoic acids. In vitro studies provide further insights ...

Abstract	Albicidin is a potent DNA gyrase inhibitor produced by the sugarcane pathogenic bacterium Xanthomonas albilineans. Here we report the elucidation of the hitherto unknown structure of albicidin, revealing a unique polyaromatic oligopeptide mainly composed of p-aminobenzoic acids. In vitro studies provide further insights into the biosynthetic machinery of albicidin. These findings will enable structural investigations on the inhibition mechanism of albicidin and its assessment as a highly effective antibacterial drug.
MeSH term(s)	4-Aminobenzoic Acid/chemistry ; Alanine/analogs & derivatives ; Alanine/chemistry ; Anti-Bacterial Agents/chemical synthesis ; Anti-Bacterial Agents/chemistry ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects ; Fermentation ; Microbial Sensitivity Tests ; Oligopeptides/chemistry ; Organic Chemicals/chemical synthesis ; Organic Chemicals/chemistry ; Organic Chemicals/pharmacology ; Structure-Activity Relationship ; Topoisomerase II Inhibitors/chemistry ; Topoisomerase II Inhibitors/pharmacology ; Xanthomonas/chemistry
Chemical Substances	Anti-Bacterial Agents ; Oligopeptides ; Organic Chemicals ; Topoisomerase II Inhibitors ; 3-cyanoalanine (923-01-3) ; albicidin (96955-97-4) ; Alanine (OF5P57N2ZX) ; 4-Aminobenzoic Acid (TL2TJE8QTX)
Language	English
Publishing date	2015-03
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2202962-X
ISSN	1552-4469 ; 1552-4450
ISSN (online)	1552-4469
ISSN	1552-4450
DOI	10.1038/nchembio.1734
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Zs.A 6251: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 2021: Bestellungen von Artikeln über das Online-Bestellformular ab Jg. 2022: Lesesaal (EG)
Zs.MG 90: Show issues

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Article ; Online: Novel Heat Shock Protein 90 Inhibitors Suppress P-Glycoprotein Activity and Overcome Multidrug Resistance in Cancer Cells.

Dinić, Jelena / Podolski-Renić, Ana / Jovanović, Mirna / Musso, Loana / Tsakovska, Ivanka / Pajeva, Ilza / Dallavalle, Sabrina / Pešić, Milica

International journal of molecular sciences

2019 Volume 20, Issue 18

Abstract: ... responsible for multidrug resistance (MDR) such as P-glycoprotein (P-gp). Recognizing the potential of new ... compounds to inhibit P-gp function and/or expression is essential in the search for effective anticancer ... in two MDR models comprised of sensitive and corresponding resistant cancer cells with P ...

Abstract	Heat Shock Protein 90 (Hsp90) chaperone interacts with a broad range of client proteins involved in cancerogenesis and cancer progression. However, Hsp90 inhibitors were unsuccessful as anticancer agents due to their high toxicity, lack of selectivity against cancer cells and extrusion by membrane transporters responsible for multidrug resistance (MDR) such as P-glycoprotein (P-gp). Recognizing the potential of new compounds to inhibit P-gp function and/or expression is essential in the search for effective anticancer drugs. Eleven Hsp90 inhibitors containing an isoxazolonaphtoquinone core were synthesized and evaluated in two MDR models comprised of sensitive and corresponding resistant cancer cells with P-gp overexpression (human non-small cell lung carcinoma and colorectal adenocarcinoma). We investigated the effect of Hsp90 inhibitors on cell growth inhibition, P-gp activity and P-gp expression. Structure-activity relationship analysis was performed in respect to cell growth and P-gp inhibition. Compounds 5, 7, and 9 directly interacted with P-gp and inhibited its ATPase activity. Their potential P-gp binding site was identified by molecular docking studies. In addition, these compounds downregulated P-gp expression in MDR colorectal carcinoma cells, showed good relative selectivity towards cancer cells, while compound 5 reversed resistance to doxorubicin and paclitaxel in concentration-dependent manner. Therefore, compounds 5, 7 and 9 could be promising candidates for treating cancers with P-gp overexpression.
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry ; ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Antineoplastic Agents/chemistry ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Neoplasm/drug effects ; Gene Expression Profiling ; HSP90 Heat-Shock Proteins/antagonists & inhibitors ; HSP90 Heat-Shock Proteins/chemistry ; HSP90 Heat-Shock Proteins/genetics ; Humans ; Models, Molecular ; Molecular Conformation ; Molecular Structure ; Structure-Activity Relationship
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Antineoplastic Agents ; HSP90 Heat-Shock Proteins
Language	English
Publishing date	2019-09-16
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms20184575
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Sulfocoumarins, specific carbonic anhydrase IX and XII inhibitors, interact with cancer multidrug resistant phenotype through pH regulation and reverse P-glycoprotein mediated resistance.

Podolski-Renić, Ana / Dinić, Jelena / Stanković, Tijana / Jovanović, Mirna / Ramović, Amra / Pustenko, Aleksandrs / Žalubovskis, Raivis / Pešić, Milica

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

2019 Volume 138, Page(s) 105012

Abstract: New 6-triazolyl-substituted sulfocoumarins were described as potent inhibitors of the transmembrane human carbonic anhydrase isoforms, CAIX and CAXII. These membrane associated enzymes that maintain pH and ... ...

Abstract	New 6-triazolyl-substituted sulfocoumarins were described as potent inhibitors of the transmembrane human carbonic anhydrase isoforms, CAIX and CAXII. These membrane associated enzymes that maintain pH and CO
MeSH term(s)	ATP Binding Cassette Transporter, Subfamily B, Member 1/metabolism ; Carbonic Anhydrase IX/antagonists & inhibitors ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Drug Resistance, Multiple/drug effects ; Drug Resistance, Neoplasm/drug effects ; Enzyme Inhibitors/pharmacology ; Homeostasis/drug effects ; Humans ; Hydrogen-Ion Concentration/drug effects ; Neoplasms/drug therapy ; Neoplasms/metabolism ; Phenotype
Chemical Substances	ATP Binding Cassette Transporter, Subfamily B, Member 1 ; Enzyme Inhibitors ; Carbonic Anhydrase IX (EC 4.2.1.1)
Language	English
Publishing date	2019-07-19
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1154366-8
ISSN	1879-0720 ; 0928-0987
ISSN (online)	1879-0720
ISSN	0928-0987
DOI	10.1016/j.ejps.2019.105012
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Article ; Online: DTA0100, dual topoisomerase II and microtubule inhibitor, evades paclitaxel resistance in P-glycoprotein overexpressing cancer cells.

Podolski-Renić, Ana / Banković, Jasna / Dinić, Jelena / Ríos-Luci, Carla / Fernandes, Miguel X / Ortega, Nuria / Kovačević-Grujičić, Nataša / Martín, Víctor S / Padrón, José M / Pešić, Milica

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences

2017 Volume 105, Page(s) 159–168

Abstract: ... by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β ... cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma ... the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant ...

Abstract	The efficacy of microtubule targeting agents in cancer treatment has been compromised by the development of drug resistance that may involve both, P-glycoprotein overexpression and the changes in β-tubulin isoforms' expression. The anti-Topoisomerase II activity of methyl 4-((E)-2-(methoxycarbonyl)vinyloxy)oct-2-ynoate (DTA0100) was recently reported. Herein, we further evaluated this propargylic enol ether derivative and found that it exerts inhibitory effect on tubulin polymerization by binding to colchicine binding site. DTA0100 mitotic arrest properties were investigated in two multi-drug resistant cancer cell lines with P-glycoprotein overexpression (colorectal carcinoma and glioblastoma). The sensitivity of multi-drug resistant cancer cell lines to DTA0100 was not significantly changed in contrast to microtubule targeting agents such as paclitaxel, vinblastine and colchicine. DTA0100 clearly induced microtubule depolymerization, leading to disturbance of cell cycle kinetics and subsequent apoptosis. The fine-tuning in β-tubulin isoforms expression observed in multi-drug resistant cancer cells may influence the efficacy of DTA0100. Importantly, DTA0100 blocked the P-glycoprotein function in both multi-drug resistant cancer cell lines without inducing the increase in P-glycoprotein expression. Therefore, DTA0100 acting as dual inhibitor of Topoisomerase II and microtubule formation could be considered as multi-potent anticancer agent. Besides, it is able to overcome the problem of drug resistance that emerges in the therapeutic approaches with either Topoisomerase II or microtubule targeting agents.
Language	English
Publishing date	2017-07-15
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	1154366-8
ISSN	1879-0720 ; 0928-0987
ISSN (online)	1879-0720
ISSN	0928-0987
DOI	10.1016/j.ejps.2017.05.011
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Article ; Online: Novel Heat Shock Protein 90 Inhibitors Suppress P-Glycoprotein Activity and Overcome Multidrug Resistance in Cancer Cells

Jelena Dinić / Ana Podolski-Renić / Mirna Jovanović / Loana Musso / Ivanka Tsakovska / Ilza Pajeva / Sabrina Dallavalle / Milica Pešić

International Journal of Molecular Sciences, Vol 20, Iss 18, p

2019 Volume 4575

Abstract	Heat Shock Protein 90 (Hsp90) chaperone interacts with a broad range of client proteins involved in cancerogenesis and cancer progression. However, Hsp90 inhibitors were unsuccessful as anticancer agents due to their high toxicity, lack of selectivity against cancer cells and extrusion by membrane transporters responsible for multidrug resistance (MDR) such as P-glycoprotein (P-gp). Recognizing the potential of new compounds to inhibit P-gp function and/or expression is essential in the search for effective anticancer drugs. Eleven Hsp90 inhibitors containing an isoxazolonaphtoquinone core were synthesized and evaluated in two MDR models comprised of sensitive and corresponding resistant cancer cells with P-gp overexpression (human non-small cell lung carcinoma and colorectal adenocarcinoma). We investigated the effect of Hsp90 inhibitors on cell growth inhibition, P-gp activity and P-gp expression. Structure−activity relationship analysis was performed in respect to cell growth and P-gp inhibition. Compounds 5, 7, and 9 directly interacted with P-gp and inhibited its ATPase activity. Their potential P-gp binding site was identified by molecular docking studies. In addition, these compounds downregulated P-gp expression in MDR colorectal carcinoma cells, showed good relative selectivity towards cancer cells, while compound 5 reversed resistance to doxorubicin and paclitaxel in concentration-dependent manner. Therefore, compounds 5, 7 and 9 could be promising candidates for treating cancers with P-gp overexpression.
Keywords	isoxazolonaphthoquinones ; Hsp90 inhibitors ; P-glycoprotein inhibitors ; cancer ; multidrug resistance ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Language	English
Publishing date	2019-09-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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