Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma

Bates, Andrew C.; Klugh, Kameron L.; Galaeva, Anna O.; Patch, Raley A.; Manganaro, John F.; Markham, Skyler A.; Scurek, Emma; Levina, Aviva; Lay, Peter A.; Crans, Debbie C.

doi:10.3390/ijms26030994

This is an early access version, the complete PDF, HTML, and XML versions will be available soon.

Open AccessArticle

Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma

by

Andrew C. Bates

¹

,

Kameron L. Klugh

¹,

Anna O. Galaeva

¹,

Raley A. Patch

¹,

John F. Manganaro

¹,

Skyler A. Markham

¹,

Emma Scurek

¹,

Aviva Levina

²

,

Peter A. Lay

^2,*

and

Debbie C. Crans

^1,3,*

¹

Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA

²

School of Chemistry, The University of Sydney, Sydney, NSW 2006, Australia

³

Cell and Molecular Biology Program, Colorado State University, Fort Collins, CO 80523, USA

^*

Authors to whom correspondence should be addressed.

Int. J. Mol. Sci. 2025, 26(3), 994; https://doi.org/10.3390/ijms26030994

Submission received: 11 December 2024 / Revised: 16 January 2025 / Accepted: 20 January 2025 / Published: 24 January 2025

(This article belongs to the Special Issue Novel Strategies in the Development of New Therapies, Drug Substances and Drug Carriers, 3rd Edition)

Download Versions Notes

Abstract

Glioblastoma, an aggressive cancer, is difficult to treat due to its location, late detection, drug resistance, and poor absorption of chemotherapeutics. Intratumoral drug administration offers a promising potential treatment alternative with localized delivery and minimal systemic toxicity. Vanadium(V) coordination complexes, incorporating Schiff base and catecholate ligands, have shown effects as antiproliferative agents with tunable efficacy and reactivity, stability, steric bulk, hydrophobicity, uptake, and toxicity optimized for the intratumoral administration vehicle. A new series of oxovanadium(V) Schiff base–catecholate complexes were synthesized and characterized using nuclear magnetic resonance (NMR), UV-Vis, and infrared spectroscopy and mass spectrometry. Stability under physiological conditions was assessed via UV-Vis spectroscopy, and the antiproliferative activity was evaluated in T98G glioblastoma and SVG p12 normal glial cells using viability assays. The newly synthesized [VO(3-tBuHSHED)(TIPCAT)] complex was more stable (t_1/2 ~ 4.5 h) and had strong antiproliferative activity (IC₅₀ ~ 1.5 µM), comparing favorably with the current lead compound, [VO(HSHED)(DTB)]. The structural modifications enhanced stability, hydrophobicity, and steric bulk through substitution with iso-propyl and tert-butyl groups. The improved properties were attributed to steric hindrance associated with the new Schiff base and catecholato ligands, as well as the formation of non-toxic byproducts upon degradation. The [VO(3-tBuHSHED)(TIPCAT)] complex emerges as a promising candidate for glioblastoma therapy by demonstrating enhanced stability and a greater selectivity, which highlights the role of strategic ligand design in developing localized therapies for the treatment of resistant cancers. In reporting the new class of compounds effective against T98G glioblastoma cells, we describe the generally desirable properties that potential drugs being developed for intratumoral administration should have.

Keywords: innovative chemotherapeutic agents; cancer; intratumoral injection; glioblastoma; optimizing drugs for intratumoral injection; vanadium; oxovanadium Schiff base catecholate complexes; sterically hindered catechol; hydrophobic Schiff base scaffold

Share and Cite

MDPI and ACS Style

Bates, A.C.; Klugh, K.L.; Galaeva, A.O.; Patch, R.A.; Manganaro, J.F.; Markham, S.A.; Scurek, E.; Levina, A.; Lay, P.A.; Crans, D.C. Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma. Int. J. Mol. Sci. 2025, 26, 994. https://doi.org/10.3390/ijms26030994

AMA Style

Bates AC, Klugh KL, Galaeva AO, Patch RA, Manganaro JF, Markham SA, Scurek E, Levina A, Lay PA, Crans DC. Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma. International Journal of Molecular Sciences. 2025; 26(3):994. https://doi.org/10.3390/ijms26030994

Chicago/Turabian Style

Bates, Andrew C., Kameron L. Klugh, Anna O. Galaeva, Raley A. Patch, John F. Manganaro, Skyler A. Markham, Emma Scurek, Aviva Levina, Peter A. Lay, and Debbie C. Crans. 2025. "Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma" International Journal of Molecular Sciences 26, no. 3: 994. https://doi.org/10.3390/ijms26030994

APA Style

Bates, A. C., Klugh, K. L., Galaeva, A. O., Patch, R. A., Manganaro, J. F., Markham, S. A., Scurek, E., Levina, A., Lay, P. A., & Crans, D. C. (2025). Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma. International Journal of Molecular Sciences, 26(3), 994. https://doi.org/10.3390/ijms26030994

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Optimizing Therapeutics for Intratumoral Cancer Treatments: Antiproliferative Vanadium Complexes in Glioblastoma

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI