Recent Progresses in Conjugation with Bioactive Ligands to Improve the Anticancer Activity of Platinum Compounds

Abstract

: Platinum (Pt) drugs, including cisplatin, are widely used for the treatment of solid tumors. Despite the clinical success, side effects and occurrence of resistance represent major limitations to the use of clinically available Pt drugs. To overcome these problems, a variety of derivatives have been designed and synthetized. Here, we summarize the recent progress in the development of Pt(II) and Pt(IV) complexes with bioactive ligands. The development of Pt(II) and Pt(IV) complexes with targeting molecules, clinically available agents, and other bioactive molecules is an active field of research. Even if none of the reported Pt derivatives has been yet approved for clinical use, many of these compounds exhibit promising anticancer activities with an improved pharmacological profile. Thus, planning hybrid compounds can be considered as a promising approach to improve the available Pt-based anticancer agents and to obtain new molecular tools to deepen the knowledge of cancer progression and drug resistance mechanisms.

Iodide n,π-chelate complexes of platinum(II) based on N-allyl substituted thioureas and their effect on the activity of hepatobiliary system enzymes in comparison with chloride analogs

“…These absorption bands undergo both bathochromic and hypsochromic shifts of +20/21 and - (10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) nm relative to their chloride counterparts (green curves in Fig. 2) studied in our previous publications [17,19].…”

“…A recent trend in the development of new metal-based anticancer drugs is the use of biologically active ligands capable of inhibiting the growth of malignant tumors with different mechanisms of action [10,11]. Promising ligands for the development of new potential drugs are thiourea derivatives, which, having high antitumor activity [12], are able to coordinate many metal ions as N,S donor agents [13][14][15].…”

The Strange Case: The Unsymmetric Cisplatin‐Based Pt(IV) Prodrug [Pt(CH3COO)Cl2(NH3)2(OH)] Exhibits Higher Cytotoxic Activity with respect to Its Symmetric Congeners due to Carrier‐Mediated Cellular Uptake

“…Tetraplatin (also named ormaplatin, (OC-6-22)-tetrachlorido(cyclohexane-1R,2R-diamine)platinum(IV)), ipr oplatin [(OC-6-33)-bis(hydroxido)dichloridodiiso propylamineplatinum(IV)], satraplatin [(OC-6-43)-bis(acetato)amminedichloridocyclohexylamineplatinum(IV)], and LA-12 [(OC-6-43)-bis(acetato)(1-adamantylamine)amminedichloridoplatinum(IV)] have progressed to preclinical studies and clinical trials, although none of them has been approved for clinical use [5][6][7][8][9]. Furthermore, the rational design of biaction or multiaction Pt(IV) prodrugs based on the insertion of biologically active ligands in the axial positions (generally through their carboxylate functionality), acting as auxiliary drugs (ideally synergistic with cisplatin), improves their targeting and cellular accumulation, generating or stimulating the immune response or antimetastatic activity, and often overcomes Pt chemoresistance [10][11][12][13][14][15][16][17][18][19].…”