{rfName}
Bi

Indexed in

Citations

30

Altmetrics

Analysis of institutional authors

Hicke, Francisco JAuthor

Share

January 19, 2025
Publications
>
Article
No

Biotinylated selenocyanates: Potent and selective cytostatic agents

Publicated to: Bioorganic Chemistry. 133 106410- - 2023-02-21 133(), DOI: 10.1016/j.bioorg.2023.106410

Authors:

Roldan-Pena, Jesus M; Puerta, Adrian; Dinic, Jelena; Stojanov, Sofija Jovanovic; Gonzalez-Bakker, Aday; Hicke, Francisco J; Mishra, Atreyee; Piyasaengthong, Akkharadet; Maya, Ines; Walton, James W; Pesic, Milica; Padron, Jose M; Fernandez-Bolanos, Jose G; Lopez, Oscar
[+]

Affiliations

Kasetsart Univ, Fac Sci, Biosci Program, Bangkok 10900, Chatuchak, Thailand - Author
Univ Belgrade, Inst Biol Res Sinisa Stankovic, Natl Inst Republ Serbia, Despota Stefana 142, Belgrade 11060, Serbia - Author
Univ Durham, Dept Chem, South Rd, Durham DH1 3LE, England - Author
Univ La Laguna, Inst Univ Bioorgan Antonio Gonzalez IUBO AG, BioLab, Astrofis Francisco Sanchez 2, E-38206 San Cristobal la Laguna, Spain - Author
Univ Seville, Fac Chem, Organ Chem Dept, POB 1203, Seville 41071, Spain - Author
See more

Abstract

Most of the currently available cytotoxic agents for tackling cancer are devoid of selectivity, thus causing severe side-effects. This situation stimulated us to develop new antiproliferative agents with enhanced affinity towards tumour cells. We focused our attention on novel chalcogen-containing compounds (thiosemicarbazones, disul-fides, selenoureas, thio-and selenocyanates), and particularly on selenium derivatives, as it has been docu-mented that this kind of compounds might act as prodrugs releasing selenium-based reactive species on tumour cells. Particularly interesting in terms of potency and selectivity was a pharmacophore comprised by a selenocyanato-alkyl fragment connected to a p-phenylenediamine residue, where the nature of the second amino moiety (free, Boc-protected, enamine-protected) provided a wide variety of antiproliferative activities, ranging from the low micromolar to the nanomolar values. The optimized structure was in turn conjugated through a peptide linkage with biotin (vitamin B7), a cellular growth promoter, whose receptor is overexpressed in numerous cancer cells; the purpose was to develop a selective vector towards malignant cells. Such biotinylated derivative behaved as a very strong antiproliferative agent, achieving GI50 values in the low nM range for most of the tested cancer cells; moreover, it was featured with an outstanding selectivity, with GI50 > 100 mu M against human fibroblasts. Mechanistic studies on the mode of inhibition of the biotinylated selenocyanate revealed (Annexin-V assay) a remarkable increase in the number of apoptotic cells compared to the control experiment; moreover, depolari-zation of the mitochondrial membrane was detected by flow cytometry analysis, and with fluorescent micro-scopy, what supports the apoptotic cell death. Prior to the apoptotic events, cytostatic effects were observed against SW1573 cells using label-free cell-living imaging; therefore, tumour cell division was prevented. Multidrug resistant cell lines exhibited a reduced sensitivity towards the biotinylated selenocyanate, probably due to its P-gp-mediated efflux. Remarkably, antiproliferative levels could be restored by co-administration with tariquidar, a P-gp inhibitor; this approach can, therefore, overcome multidrug resistance mediated by the P-gp efflux system.
[+]

Keywords

AnticancerAntineoplastic agentsAntiproliferativeApoptosisBiotinCell line, tumorCell proliferationCyanatesCytostatic agenCytostatic agentCytostatic agentsHumansOrganochalcogenSeleniumSelenocyanateSelenocyanic acidSelenosemicarbazoneStructure-activity relationship

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Bioorganic Chemistry due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2023, it was in position 7/58, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Organic.

From a relative perspective, and based on the normalized impact indicator calculated from World Citations provided by WoS (ESI, Clarivate), it yields a value for the citation normalization relative to the expected citation rate of: 1.67. This indicates that, compared to works in the same discipline and in the same year of publication, it ranks as a work cited above average. (source consulted: ESI Nov 13, 2025)

This information is reinforced by other indicators of the same type, which, although dynamic over time and dependent on the set of average global citations at the time of their calculation, consistently position the work at some point among the top 50% most cited in its field:

  • Weighted Average of Normalized Impact by the Scopus agency: 1.05 (source consulted: FECYT Mar 2025)

Specifically, and according to different indexing agencies, this work has accumulated citations as of 2026-01-31, the following number of citations:

  • WoS: 11
  • Scopus: 8
  • Europe PMC: 7
[+]

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2026-01-31:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 10.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 10 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 8.
  • The number of mentions on the social network X (formerly Twitter): 9 (Altmetric).
[+]

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: Serbia; Thailand; United Kingdom.

[+]

Awards linked to the item

We thank Grant PID2020-116460RB-I00 funded by MCIN/AEI/10.13039/501100011033, and Junta de Andalucia (FQM134) for financial support. J.R.-P. thanks the Ministerio de Educaci'on y Ciencia for the award of a predoctoral grant. A.P., A.G.-B. and J.M.P. thank the Spanish Government (Project PID2021-123059OB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE) for financial support. A.P. thanks the EU Social Fund (FSE) and the Canary Islands ACIISI for a predoctoral grant TESIS2020010055. J.D., S.J.S. and M.P. thank the Ministry of Education, Science and Technological Development of the Republic of Serbia for financial support (451-03-68/2022-14/200007). A.P.d,e acknowledges the Thailand Development and Promotion of Science and Technology (DPST) Talents Project for funding. This work was performed within the framework of COST Action CA17104 STRAT-AGEM "New diagnostic and therapeutic tools against multidrug resistant tumors". We would also like to thank the Servicio de Resonancia Magne'tica Nuclear, CITIUS (University of Seville) for the performance of NMR experiments.
[+]