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14 pages, 3185 KiB

Open AccessArticle

Series of Organotin(IV) Compounds with Different Dithiocarbamate Ligands Induced Cytotoxicity, Apoptosis and Cell Cycle Arrest on Jurkat E6.1, T Acute Lymphoblastic Leukemia Cells

by Nur Rasyiqin Rasli, Asmah Hamid, Normah Awang and Nurul Farahana Kamaludin

Molecules 2023, 28(8), 3376; https://doi.org/10.3390/molecules28083376 - 11 Apr 2023

Cited by 6 | Viewed by 1814

Abstract

The discovery of cisplatin has influenced scientists to study the anticancer properties of other metal complexes. Organotin(IV) dithiocarbamate compounds are gaining attention as anticancer agents due to their potent cytotoxic properties on cancer cells. In this study, a series of organotin compounds were [...] Read more.

The discovery of cisplatin has influenced scientists to study the anticancer properties of other metal complexes. Organotin(IV) dithiocarbamate compounds are gaining attention as anticancer agents due to their potent cytotoxic properties on cancer cells. In this study, a series of organotin compounds were assessed for their toxic effects on the Jurkat E6.1 cell line. WST-1 assay was used to determine the cytotoxic effect of the compounds and showed that six out of seven organotin(IV) dithiocarbamate compounds exhibited potent cytotoxic effects toward T-lymphoblastic leukemia cells, Jurkat E6.1 with the concentration of IC₅₀ ranging from 0.67–0.94 µM. The apoptosis assay by Annexin V-FITC/PI staining showed that all tested compounds induced cell death mainly via apoptosis. Cell cycle analysis assessed using RNase/PI staining showed that organotin(IV) dithiocarbamate compounds induced cell cycle arrest at different phases. In conclusion, the tested organotin(IV) dithiocarbamate compounds demonstrated potent cytotoxicity against Jurkat E6.1 cells via apoptosis and cell cycle arrest at low IC₅₀ value. However, further studies on the mechanisms of action are required to probe the possible potential of these compounds on leukemia cells before they can be developed into anti-leukemic agents. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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14 pages, 1566 KiB

Open AccessFeature PaperArticle

Exploring pta Alternatives in the Development of Ruthenium–Arene Anticancer Compounds

by Jakob Kljun, Mihaela Rebernik, Lucía M. Balsa, Jerneja Kladnik, Uroš Rapuš, Tomaž Trobec, Kristina Sepčić, Robert Frangež, Ignacio E. León and Iztok Turel

Molecules 2023, 28(6), 2499; https://doi.org/10.3390/molecules28062499 - 9 Mar 2023

Cited by 1 | Viewed by 1959

Abstract

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η⁶-p-cymene)Ru(pyrithionato)(pta)]PF₆ contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the [...] Read more.

Organoruthenium pyrithione (1-hydroxypyridine-2-thione) complexes have been shown in our recent studies to be a promising family of compounds for development of new anticancer drugs. The complex [(η⁶-p-cymene)Ru(pyrithionato)(pta)]PF₆ contains phosphine ligand pta (1,3,5-triaza-7-phosphaadamantane) as a functionality that improves the stability of the complex and its aqueous solubility. Here, we report our efforts to find pta alternatives and discover new structural elements to improve the biological properties of ruthenium anticancer drugs. The pta ligand was replaced by a selection of phosphine, phosphite, and arsine ligands to identify new functionalities, leading to improvement in inhibitory potency towards enzyme glutathione S-transferase. In addition, cytotoxicity in breast, bone, and colon cancers was investigated. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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13 pages, 2079 KiB

Open AccessArticle

A Non-Conventional Platinum Drug against a Non-Small Cell Lung Cancer Line

by Jéssica D. Silva, Joana Marques, Inês P. Santos, Ana L. M. Batista de Carvalho, Clara B. Martins, Raquel C. Laginha, Luís A. E. Batista de Carvalho and Maria Paula M. Marques

Molecules 2023, 28(4), 1698; https://doi.org/10.3390/molecules28041698 - 10 Feb 2023

Cited by 1 | Viewed by 2027

Abstract

A dinuclear Pt(II) complex with putrescine as bridging polyamine ligand ([Pt₂Put₂(NH₃)₄]Cl₄) was synthesized and assessed as to its potential anticancer activity against a human non-small cell lung cancer line (A549), as well as [...] Read more.

A dinuclear Pt(II) complex with putrescine as bridging polyamine ligand ([Pt₂Put₂(NH₃)₄]Cl₄) was synthesized and assessed as to its potential anticancer activity against a human non-small cell lung cancer line (A549), as well as towards non-cancer cells (BEAS-2B). This effect was evaluated through in vitro cytotoxicity assays (MTT and SRB) coupled to microFTIR and microRaman spectroscopies, the former delivering information on growth-inhibiting and cytotoxic abilities while the latter provided very specific information on the metabolic impact of the metal agent (at the sub-cellular level). Regarding cancer cells, a major impact of [Pt₂Put₂(NH₃)₄]Cl₄ was evidenced on cellular proteins and lipids, as compared to DNA, particularly via the Amide I and Amide II signals. The effect of the chelate on non-malignant cells was lower than on malignant ones, evidencing a promising low toxicity towards healthy cells. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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14 pages, 1723 KiB

Open AccessArticle

New Copper(II)-L-Dipeptide-Bathophenanthroline Complexes as Potential Anticancer Agents—Synthesis, Characterization and Cytotoxicity Studies—And Comparative DNA-Binding Study of Related Phen Complexes

by Carlos Y. Fernández, Natalia Alvarez, Analu Rocha, Javier Ellena, Antonio J. Costa-Filho, Alzir A. Batista and Gianella Facchin

Molecules 2023, 28(2), 896; https://doi.org/10.3390/molecules28020896 - 16 Jan 2023

Cited by 15 | Viewed by 2695

Abstract

Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in [...] Read more.

Searching for new copper compounds which may be useful as antitumor drugs, a series of new [Cu(L-dipeptide)(batho)] (batho:4,7-diphenyl-1,10-phenanthroline, L-dipeptide: Gly-Val, Gly-Phe, Ala-Gly, Ala-Ala, Ala-Phe, Phe-Ala, Phe-Val and Phe-Phe) complexes were synthesized and characterized. To interpret the experimental IR spectra, [Cu(ala-gly)(batho)] was modelled in the gas phase using DFT at the B3LYP/LANL2DZ level of theory and the calculated vibrational frequencies were analyzed. Solid-state characterization is in agreement with pentacoordinate complexes of the general formula [Cu(L-dipeptide)(batho)]·x solvent, similar to other [Cu(L-dipeptide)(diimine)] complexes. In solution, the major species are heteroleptic, as in the solid state. The mode of binding to the DNA was evaluated by different techniques, to understand the role of the diimine and the dipeptide. To this end, studies were also performed with complexes [CuCl₂(diimine)], [Cu(L-dipeptide)(diimine)] and free diimines, with phenanthroline, neocuproine and 3,4,7,8-tetramethyl-phenanthroline. The cytotoxicity of the complexes was determined on human cancer cell lines MDA-MB-231, MCF-7 (breast, the first triple negative), and A549 (lung epithelial) and non-tumor cell lines MRC-5 (lung) and MCF-10A (breast). [Cu(L-dipeptide)(batho)] complexes are highly cytotoxic as compared to cisplatin and [Cu(L-dipeptide)(phenanthroline)] complexes, being potential candidates to study their in vivo activity in the treatments of aggressive tumors for which there is no curative pharmacological treatment. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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19 pages, 1950 KiB

Open AccessArticle

Synthesis of Some Mono- and Disaccharide-Grafting Phthalazine Derivatives and Some New Se-Nucleoside Analogues: Antibacterial Properties, Quantum Chemical Calculations, and Cytotoxicity

by I. E. El-Shamy, E. Hleli, A. A. Alsheikh, M. A. Yawer, M. A. El-Hashash, J. Dybal and A. M. Abdel-Mohsen

Molecules 2023, 28(1), 317; https://doi.org/10.3390/molecules28010317 - 30 Dec 2022

Cited by 3 | Viewed by 2158

Abstract

A highly efficient and versatile synthetic approach for the synthesis of 4-(pyren-1-ylmethyl)-1-(d-glycosyloxy) phthalazine nucleosides 11a,b, 13, β-S-nucleosides 16, 18, 20, and acyclo C-nucleosides 23a,b, 24, 25 [...] Read more.

A highly efficient and versatile synthetic approach for the synthesis of 4-(pyren-1-ylmethyl)-1-(d-glycosyloxy) phthalazine nucleosides 11a,b, 13, β-S-nucleosides 16, 18, 20, and acyclo C-nucleosides 23a,b, 24, 25 and 27a–f was described and fully characterized. Furthermore, a series of desired new nucleoside analogues containing Se of 4-(pyren-1-ylmethyl) phthalazine-1(2H)-selenone 28–33 were synthesized. The structures of all reported compounds were confirmed by IR, ¹H-NMR, ¹³C-NMR, MS and elemental analysis. All compounds have been screened for their antibacterial and antifungal activities. Maximum activity was shown by 20 and 33a comparable to the standard drugs with lower toxicity. The cytotoxicity of the selected compound was measured and evaluated. The energy gap between the highest occupied molecular orbital and lowest unoccupied molecular orbital was calculated using theoretical computations to reflect the chemical reactivity and kinetic stability of the synthesized compounds. Using density functional theory (DFT), electronic parameters such as the highest occupied and lowest unoccupied molecular orbitals (HOMO and LUMO) and the molecular electrostatic potential (MEPS) were calculated. On the basis of different studied structures, these properties were computed in order to elucidate the chemical reactivity and the kinetic stability. Obviously, the band gap energy (Eg) of structures studied reveals that the lowest band gap obtained for the structure 16-a indicates that it has the highest chemical reactivity and lowest kinetic stability. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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23 pages, 3784 KiB

Open AccessArticle

Antiproliferative Homoleptic and Heteroleptic Phosphino Silver(I) Complexes: Effect of Ligand Combination on Their Biological Mechanism of Action

by Khouloud Dammak, Marina Porchia, Michele De Franco, Mirella Zancato, Houcine Naïli, Valentina Gandin and Cristina Marzano

Molecules 2020, 25(22), 5484; https://doi.org/10.3390/molecules25225484 - 23 Nov 2020

Cited by 18 | Viewed by 3046

Abstract

A series of neutral mixed-ligand [HB(pz)₃]Ag(PR₃) silver(I) complexes (PR₃ = tertiary phosphine, [HB(pz)₃]⁻ = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR₃)₄]BF₄ compounds have been synthesized and fully characterized. Silver compounds [...] Read more.

A series of neutral mixed-ligand [HB(pz)₃]Ag(PR₃) silver(I) complexes (PR₃ = tertiary phosphine, [HB(pz)₃]⁻ = tris(pyrazolyl)borate anion), and the corresponding homoleptic [Ag(PR₃)₄]BF₄ compounds have been synthesized and fully characterized. Silver compounds were screened for their antiproliferative activities against a wide panel of human cancer cells derived from solid tumors and endowed with different platinum drug sensitivity. Mixed-ligand complexes were generally more effective than the corresponding homoleptic derivatives, but the most active compounds were [HB(pz)₃]Ag(PPh₃) (5) and [Ag(PPh₃)₄]BF₄ (10), both comprising the lipophilic PPh₃ phosphine ligand. Detailed mechanistic studies revealed that both homoleptic and heteroleptic silver complexes strongly and selectively inhibit the selenoenzyme thioredoxin reductase both as isolated enzyme and in human ovarian cancer cells (half inhibition concentration values in the nanomolar range) causing the disruption of cellular thiol-redox homeostasis, and leading to apoptotic cell death. Moreover, for heteroleptic Ag(I) derivatives, an additional ability to damage nuclear DNA has been detected. These results confirm the importance of the type of silver ion coordinating ligands in affecting the biological behavior of the overall corresponding silver complexes, besides in terms of hydrophilic–lipophilic balance, also in terms of biological mechanism of action, such as interaction with DNA and/or thioredoxin reductase. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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Review

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21 pages, 2495 KiB

Open AccessReview

Combining Copper and Zinc into a Biosensor for Anti-Chemoresistance and Achieving Osteosarcoma Therapeutic Efficacy

by Yan Yik Lim, Ahmad Mujahid Ahmad Zaidi and Azizi Miskon

Molecules 2023, 28(7), 2920; https://doi.org/10.3390/molecules28072920 - 24 Mar 2023

Cited by 19 | Viewed by 2946

Abstract

Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, [...] Read more.

Due to its built-up chemoresistance after prolonged usage, the demand for replacing platinum in metal-based drugs (MBD) is rising. The first MBD approved by the FDA for cancer therapy was cisplatin in 1978. Even after nearly four and a half decades of trials, there has been no significant improvement in osteosarcoma (OS) therapy. In fact, many MBD have been developed, but the chemoresistance problem raised by platinum remains unresolved. This motivates us to elucidate the possibilities of the copper and zinc (CuZn) combination to replace platinum in MBD. Thus, the anti-chemoresistance properties of CuZn and their physiological functions for OS therapy are highlighted. Herein, we summarise their chelators, main organic solvents, and ligand functions in their structures that are involved in anti-chemoresistance properties. Through this review, it is rational to discuss their ligands’ roles as biosensors in drug delivery systems. Hereafter, an in-depth understanding of their redox and photoactive function relationships is provided. The disadvantage is that the other functions of biosensors cannot be elaborated on here. As a result, this review is being developed, which is expected to intensify OS drugs with higher cure rates. Nonetheless, this advancement intends to solve the major chemoresistance obstacle towards clinical efficacy. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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41 pages, 5436 KiB

Open AccessReview

Zinc Complexes with Nitrogen Donor Ligands as Anticancer Agents

by Marina Porchia, Maura Pellei, Fabio Del Bello and Carlo Santini

Molecules 2020, 25(24), 5814; https://doi.org/10.3390/molecules25245814 - 9 Dec 2020

Cited by 94 | Viewed by 8377

Abstract

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one [...] Read more.

The search for anticancer metal-based drugs alternative to platinum derivatives could not exclude zinc derivatives due to the importance of this metal for the correct functioning of the human body. Zinc, the second most abundant trace element in the human body, is one of the most important micro-elements essential for human physiology. Its ubiquity in thousands of proteins and enzymes is related to its chemical features, in particular its lack of redox activity and its ability to support different coordination geometries and to promote fast ligands exchange. Analogously to other trace elements, the impairment of its homeostasis can lead to various diseases and in some cases can be also related to cancer development. However, in addition to its physiological role, zinc can have beneficial therapeutic and preventive effects on infectious diseases and, compared to other metal-based drugs, Zn(II) complexes generally exert lower toxicity and offer few side effects. Zinc derivatives have been proposed as antitumor agents and, among the great number of zinc coordination complexes which have been described so far, this review focuses on the design, synthesis and biological studies of zinc complexes comprising N-donor ligands and that have been reported within the last five years. Full article

(This article belongs to the Special Issue Metal-Based Drugs Ⅱ)

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