G. Gencheva

Bio: G. Gencheva is an academic researcher from Sofia University. The author has contributed to research in topics: Ligand & Hematoporphyrin. The author has an hindex of 8, co-authored 32 publications receiving 190 citations.

Synthesis of New Monomeric Pd(III) and Dimeric (Pd(III),Pd(II)) Complexes with Biuret Formed in Basic Medium

Abstract: New monomeric Pd(III) and dimeric (Pd(III)-Pd(II)) paramagnetic complexes with biuret (BiuH2) were synthesized and their structures and coordination modes studied using magnetochemical and spectroscopic (EPR, IR, ESCA) methods. For the monomeric species a metal to ligand ratio 1:2 was found and for the dimeric one it was 2:3. A distorted rhombic structure was suggested for the [Pd(III)(Biu)2]− species. For the dimeric complex it was accepted that one of the biuret molecules is serving as bridging ligand coordinated via both NH-groups to one of the palladium ions and via both C=O groups to the other. A distorted rhombic structure is suggested for each of the palladium ions. Referee I: W. A. Donaldson Referee II: N. M. Kostic

Synthesis, Structural Characterization, and Cytotoxic Activity of Novel Paramagnetic Platinum Hematoporphyrin IX Complexes: Potent Antitumor Agents

Abstract: Three novel stable Pt(III) complexes with distorted octahedral structure and (dz2)1 ground state have been obtained in the course of Pt(II)-hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp) interaction in alkaline aqueous medium and aerobic conditions. A redox interaction also takes place together with the complexation process leading to the formation of Pt(III) species and organic radicals. The processes in the reaction system and the structure of the complexes formed cis-[Pt(III)(NH3)2(Hp-3H)(H2O)2]H2O1, [Pt(III)(Hp-3H)(H2O)2]H2O2, and [Pt((O,O)Hp-2H)Cl(H2O)3] 3, were studied by UV-Vis, IR, EPR and XPS spectra, thermal (TGS, DSC), potentiometric and magnetic methods. The newly synthesized complexes show promising cytotoxic activity comparable with that of cis-platin in in vitro tests against a panel of human leukemia cell lines. The observed cytotoxicity of the complex 2 against SKW-3 cells (KE-37 derivative) is due to induction of cell death through apoptosis.

In Vitro Evaluation of a Stable Monomeric Gold(II) Complex with Hematoporphyrin IX: Cytotoxicity against Tumor and Kidney Cells, Cellular Accumulation, and Induction of Apoptosis

Abstract: The antineoplastic potential of a stable monomeric Au(II) complex with hematoporphyrin IX (Hp), namely [Au(II)Hp−2H.(H2O)2], was investigated in a panel of tumor cell lines. The complex exhibits strong cytotoxicity, whereby the leukaemia- and lymphoma-derived cell lines are more sensitive, with IC50 values comparable to those of the reference anticancer drug cisplatin. In contrast, the solid tumor models are more sensitive to the platinum drug. A comparative assessment of both agents against the human kidney cell line 293T has shown that [Au(II)Hp−2H.(H2O)2] is less cytotoxic. The gold complex induces oligonucleosomal DNA fragmentation in tumour cells following 24-hour treatment and hence its cytotoxic effect is at least partly mediated by induction of apoptotic cell death. A prominent intracellular gold accumulation was detected after treating tumor cells with [Au(II)Hp−2H.(H2O)2] which shows that its putative pharmacological targets are readily accessible after a short incubation period.

Cellular Pharmacology of Palladinum(III) Hematoporphyrin IX Complexes: Solution Stability, Antineoplastic and Apoptogenic Activity, DNA Binding, and Processing of DNA-Adducts

Abstract: Two paramagnetic PdIII complexes of hematoporphyrin IX ((7,12-bis(1-hydroxyethyl)-3,8,13,17-tetramethyl-21H-23H-porphyn-2,18-dipropionic acid), Hp), namely a dinuclear one [PdIII2(Hp-3H)Cl3(H2O)5]·2PdCl2, Pd1 and a mononuclear metalloporphyrin type [PdIII(Hp-2H)Cl(H2O)]·H2O, Pd2 have been synthesized reproducibly and isolated as neutral compounds at different reaction conditions. Their structure and solution stability have been assayed by UV/Vis and EPR spectroscopy. The compounds researched have shown in vitro cell growth inhibitory effects at micromolar concentration against a panel of human tumor cell lines. A DNA fragmentation test in the HL-60 cell line has indicated that Pd1 causes comparable proapoptotic effects with regard to cisplatin but at substantially higher concentrations. Pd1 and cisplatin form intra-strand guanine bis-adducts as the palladium complex is less capable of forming DNA adducts. This demonstrates its cisplatin-dissimilar pharmacological profile. The test for efficient removal of DNA-adducts by the NER synthesis after modification of pBS plasmids with either cisplatin or Pd1 has manifested that the lesions induced by cisplatin are far better recognized and repaired compared those of Pd1. The study on the recognition and binding of the HMGB-1 protein to cisplatin or Pd1 modified DNA probes have shown that HMG proteins are less involved in the palladium agent cytotoxicity.

Monofunctional and Higher-Valent Platinum Anticancer Agents

Abstract: Platinum compounds represent one of the great success stories of metals in medicine. Following the serendipitous discovery of the anticancer activity of cisplatin by Rosenberg, a large number of cisplatin variants have been prepared and tested for their ability to kill cancer cells and inhibit tumor growth. These efforts continue today with increased realization that new strategies are needed to overcome issues of toxicity and resistance inherent to treatment by the approved platinum anticancer agents. One approach has been the use of so-called “non-traditional” platinum(II) and platinum(IV) compounds that violate the structure–activity relationships that governed platinum drug-development research for many years. Another is the use of specialized drug-delivery strategies. Here we describe recent developments from our laboratory involving monofunctional platinum(II) complexes together with a historical account of the manner by which we came to investigate these compounds and their relationship to previous...

Pt-Enhanced Mesoporous Ti3+/TiO2 with Rapid Bulk to Surface Electron Transfer for Photocatalytic Hydrogen Evolution.

Abstract: Pt-doped mesoporous Ti3+ self-doped TiO2 (Pt–Ti3+/TiO2) is in situ synthesized via an ionothermal route, by treating metallic Ti in an ionic liquid containing LiOAc, HOAc, and a H2PtCl6 aqueous solution under mild ionothermal conditions. Such Ti3+-enriched environment, as well as oxygen vacancies, is proven to be effective for allowing the in situ reduction of Pt4+ ions uniformly located in the framework of the TiO2 bulk. The photocatalytic H2 evolution of Pt–Ti3+/TiO2 is significantly higher than that of the photoreduced Pt loaded on the original TiO2 and commercial P25. Such greatly enhanced activity is due to the various valence states of Pt (Ptn+, n = 0, 2, or 3), forming Pt–O bonds embedded in the framework of TiO2 and ultrafine Pt metal nanoparticles on the surface of TiO2. Such Ptn+–O bonds could act as the bridges for facilitating the photogenerated electron transfer from the bulk to the surface of TiO2 with a higher electron carrier density (3.11 × 1020 cm–3), about 2.5 times that (1.25 × 1020 cm...