Interactions of Metal—Metal‐Bonded Antitumor Active Complexes with DNA Fragments and DNA

Abstract

This Account summarizes the DNA binding properties of anticancer active dinuclear Rh, Re, and Ru compounds. The combined results of NMR spectroscopy, X-ray crystallography, and various biochemical tools provide incontrovertible evidence that dinuclear complexes are favorably poised to bind to purine nucleobases, DNA fragments, and double-stranded DNA. Moreover, direct DNA photocleavage in vitro is effected by dirhodium compounds in the presence of electron acceptors in solution or directly attached to the dirhodium core. This research has provided valuable insight in the interactions of dinuclear compounds with DNA, knowledge that is an excellent backdrop for rational design of promising dinuclear drugs.

Liposomes loaded with a dirhenium compound and cisplatin: preparation, properties and improvedin vivoanticancer activity

“…Another promising paradigm in developing new antitumor pharmaceuticals is represented by dinuclear complexes of rhodium, ruthenium and rhenium with a paddlewheel structure (Clarke et al, 1999;Jakupec et al, 2008;Sun et al, 2007). In this work it was postulated that such species are capable of binding to DNA, thereby inhibiting DNA replication and protein synthesis (Chifotides et al, 2004;Sorasanee et al, 2003), in a manner akin to cisplatin (Chifotides & Dunbar, 2005;Guo & Sadler, 1999). Among this group, the dirhenium (III) compounds are recognized as especially promising candidates for clinical development due to their very low toxicity (Olyinik et al, 2001).…”

Rhenium–platinum antitumor systems

“…An important paradigm for the development of new antitumor pharmaceuticals is represented by dinuclear carboxylate complexes of rhodium, ruthenium and rhenium with so-called 'chinese lantern' structure [8][9][10]. It was postulated that such species could bind to DNA, inhibit DNA replication and protein synthesis [11,12] in a manner similar to cisplatin [4,13,14]. Among this group, the dirhenium(III) compounds may be recognized as especially promi sing candidates for clinical development due to their very low toxicity [15].…”

Вплив Реній-Платинової Системи У Вигляді Наноліпосом На Проліферативну Активність Ракових Клітин

“…На сьогодні існує вже велика бібліотека металорганічних сполук [17], найперспективніші з яких -диядерні карбоксилати ренію [12]. Окреме їх використання як неплатинових протипухлинних агентів показало, що вони мають значно меншу токсичність, ніж платиніди, але їх антиканцерогенний ефект не переви-щує такий цисплатину [12]. Вживання їх у комплексах із cPt на моделі карциноми Ге-рена (T8) зумовлює гальмування росту новоутворень і нормалізацію багатьох показ-ників червоної крові [20; 21].…”