Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies
IntroductionPalladium (II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three new Pd(II) complexes (2a–2c) with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antit...
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Frontiers Media S.A.
2025-07-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2025.1636477/full |
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| author | Damnjan Pantic Damnjan Pantic Nikola Mirkovic Nikola Mirkovic Tatjana Vulovic Tatjana Vulovic Danijela Jovanovic Danijela Jovanovic Stefan Jakovljevic Stefan Jakovljevic Petar Canovic Milan Zaric Radica Zivkovic Zaric Radica Zivkovic Zaric Marina Kostic Jovana Dragojevic Vera Divac Ziko Milanovic Kristina Milisavljevic Kristina Milisavljevic Marina Mitrovic Ivanka Zelen |
| author_facet | Damnjan Pantic Damnjan Pantic Nikola Mirkovic Nikola Mirkovic Tatjana Vulovic Tatjana Vulovic Danijela Jovanovic Danijela Jovanovic Stefan Jakovljevic Stefan Jakovljevic Petar Canovic Milan Zaric Radica Zivkovic Zaric Radica Zivkovic Zaric Marina Kostic Jovana Dragojevic Vera Divac Ziko Milanovic Kristina Milisavljevic Kristina Milisavljevic Marina Mitrovic Ivanka Zelen |
| author_sort | Damnjan Pantic |
| collection | DOAJ |
| description | IntroductionPalladium (II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three new Pd(II) complexes (2a–2c) with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antitumor activity against prostate cancer cells.MethodsThe Pd(II) complexes were synthesized and structurally characterized. Cytotoxicity was tested on two human prostate cancer cell lines (PC-3, DU-145) and healthy fibroblasts (MRC-5). Apoptosis induction was assessed by flow cytometry, with a focus on Bcl-2 and caspase proteins. Molecular docking was used to examine binding to the androgen receptor (AR) and apoptotic regulators (CASP3, BCL2, BAX). DNA and human serum albumin (HSA) binding were also investigated.ResultsAll complexes showed significant cytotoxicity. Notably, complex 2c exhibited more potent cytotoxic activity than cisplatin in prostate cancer cell lines, with lower IC50 values after 72 h exposure in DU-145 (7.1 µM vs. 8.2 µM) and PC-3 cells (8.6 µM vs. 21.9 µM), while showing reduced toxicity in normal MRC-5 cells (42.3 µM vs. 24.4 µM). Apoptosis was confirmed as the primary cytotoxic mechanism, involving the activation of Bcl-2 and caspases. Docking studies revealed that complex 2c had the strongest binding affinity to AR and apoptotic proteins, mediated by hydrogen bonds, π–π stacking, and hydrophobic interactions. DNA and HSA binding supported their biological relevance.ConclusionComplex 2c exhibits potent anticancer activity through the induction of apoptosis and dual targeting of the AR and apoptotic pathways, making it a promising candidate for further development of anticancer drugs. |
| format | Article |
| id | doaj-art-a496fcc35fa84adb977a52a6ef7fbb15 |
| institution | Kabale University |
| issn | 2296-2646 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Frontiers Media S.A. |
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| series | Frontiers in Chemistry |
| spelling | doaj-art-a496fcc35fa84adb977a52a6ef7fbb152025-08-20T03:50:58ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462025-07-011310.3389/fchem.2025.16364771636477Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studiesDamnjan Pantic0Damnjan Pantic1Nikola Mirkovic2Nikola Mirkovic3Tatjana Vulovic4Tatjana Vulovic5Danijela Jovanovic6Danijela Jovanovic7Stefan Jakovljevic8Stefan Jakovljevic9Petar Canovic10Milan Zaric11Radica Zivkovic Zaric12Radica Zivkovic Zaric13Marina Kostic14Jovana Dragojevic15Vera Divac16Ziko Milanovic17Kristina Milisavljevic18Kristina Milisavljevic19Marina Mitrovic20Ivanka Zelen21Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Urology, Clinic of Urology and Nephrology, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Vascular Surgery Center, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Anesthesia and Resuscitation, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Anesthesia and Resuscitation, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of General Surgery, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Clinical Pharmacology, University Clinical Center Kragujevac, Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Kragujevac, Serbia0Department of Chemistry, Faculty of Sciences, University of Kragujevac, Kragujevac, Serbia0Department of Chemistry, Faculty of Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Kragujevac, SerbiaDepartment of Science, Institute for Information Technologies, University of Kragujevac, Kragujevac, Serbia0Department of Chemistry, Faculty of Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaDepartment of Biochemistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, SerbiaIntroductionPalladium (II) complexes are promising anticancer agents with potential advantages over platinum drugs. This study aimed to synthesize and characterize three new Pd(II) complexes (2a–2c) with Schiff base ligands derived from salicylic acid and amine scaffolds, and to evaluate their antitumor activity against prostate cancer cells.MethodsThe Pd(II) complexes were synthesized and structurally characterized. Cytotoxicity was tested on two human prostate cancer cell lines (PC-3, DU-145) and healthy fibroblasts (MRC-5). Apoptosis induction was assessed by flow cytometry, with a focus on Bcl-2 and caspase proteins. Molecular docking was used to examine binding to the androgen receptor (AR) and apoptotic regulators (CASP3, BCL2, BAX). DNA and human serum albumin (HSA) binding were also investigated.ResultsAll complexes showed significant cytotoxicity. Notably, complex 2c exhibited more potent cytotoxic activity than cisplatin in prostate cancer cell lines, with lower IC50 values after 72 h exposure in DU-145 (7.1 µM vs. 8.2 µM) and PC-3 cells (8.6 µM vs. 21.9 µM), while showing reduced toxicity in normal MRC-5 cells (42.3 µM vs. 24.4 µM). Apoptosis was confirmed as the primary cytotoxic mechanism, involving the activation of Bcl-2 and caspases. Docking studies revealed that complex 2c had the strongest binding affinity to AR and apoptotic proteins, mediated by hydrogen bonds, π–π stacking, and hydrophobic interactions. DNA and HSA binding supported their biological relevance.ConclusionComplex 2c exhibits potent anticancer activity through the induction of apoptosis and dual targeting of the AR and apoptotic pathways, making it a promising candidate for further development of anticancer drugs.https://www.frontiersin.org/articles/10.3389/fchem.2025.1636477/fullpalladiumschiff basesDNAalbumincytotoxicityapoptosis |
| spellingShingle | Damnjan Pantic Damnjan Pantic Nikola Mirkovic Nikola Mirkovic Tatjana Vulovic Tatjana Vulovic Danijela Jovanovic Danijela Jovanovic Stefan Jakovljevic Stefan Jakovljevic Petar Canovic Milan Zaric Radica Zivkovic Zaric Radica Zivkovic Zaric Marina Kostic Jovana Dragojevic Vera Divac Ziko Milanovic Kristina Milisavljevic Kristina Milisavljevic Marina Mitrovic Ivanka Zelen Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies Frontiers in Chemistry palladium schiff bases DNA albumin cytotoxicity apoptosis |
| title | Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| title_full | Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| title_fullStr | Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| title_full_unstemmed | Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| title_short | Evaluation of newly synthesized schiff base Pd(II) complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| title_sort | evaluation of newly synthesized schiff base pd ii complexes for prostate cancer treatment through in vitro cytotoxicity and molecular mechanistic studies |
| topic | palladium schiff bases DNA albumin cytotoxicity apoptosis |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2025.1636477/full |
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