Current Organic Chemistry - Volume 19, Issue 10, 2015

Neopeltolide, isolated in 2007, with its novel structural features and potent anti-cancer cell proliferation activity, has attracted a tremendous amount of synthetic efforts. This review briefly and chronologically summarizes each synthesis with the main focus on the strategies and methodologies for the construction of its cistetrahydropyran- containing macrolactone core.

This review will trace the steps in the development of pixantrone dimaleate (initial code BBR 2778, Pixruvi®), an anthracenedione chemotype, as a chemotherapeutic agent. This drug exhibits reduced cardiotoxicity in comparison to anthracyclines and mitoxantrone. Synthetic pathways, biological evaluations and mechanistic considerations will be discussed. On May 10, 2012, the European Medicines Agency granted a conditional marketing approval to CTI Biopharma for pixantrone dimaleate for the treatment of adults suffering from multiple relapsed or refractory aggressive non-Hodgkin B-cell lymphomas (NHL). Potential applications of pixantrone dimaleate for the treatment of multiple sclerosis and other maladies will be presented.

Hormone-sensitive breast cancers correspond to breast tumors with the existence of estrogen and progesterone in the tumor issue. The hormones estrogen and progesterone may in some circumstance promote the growth of breast cancers. Therefore, compounds targeting hormone-sensitive breast cancers have attracted considerable interest from synthetic organic chemists. In the past two decades, numerous compounds have thus been designed and synthesized to investigate their anti-breast cancer activities. In this review, some recent synthetic endeavor in the past five years towards compounds targeting hormone-sensitive breast cancers, especially estrogenreceptor positive breast cancers, are summarized.

Pentacyclic triterpenes are natural substances, synthesized and present in variable amounts in a large number of terrestrial and aquatic plants, which act not only as antioxidants and antimicrobials but also as poisons, antibiotics, protease inhibitors, and so on. From the organic chemistry point of view, they are compounds derived from isoprene. These compounds consist of 30 carbons with different substituents, which facilitate their chemical identification and confer different physico-chemical and molecular properties. During the last ten years, most of them have been reported to have a variety of interesting and significant biological properties, such as analgesic, anti-allodynic, anti-diabetic, anti-oxidant, anti-parasitic, antimicrobial, anti-viral, anti-atherogenic, anti-inflammatory, anti-proliferative, anti-tumour, growth-stimulating activities as well as cardioand neuro-protective activity. However, special attention has been focused on the study of their anti-tumour capacity, fundamentally, on the various molecular mechanisms involved in the induction of programmed cell death and the inhibition of metastatic activity, in different types of cancers. Researchers have also focused on the role that different RNA molecules play in the anti-tumour activity of the major triterpenes studied. In this review, we look at the recent advances reported on the anti-tumorigenic roles of the main representatives of this group of compounds, such as betulinic (BA), ursolic (UA), oleanolic (OA) and maslinic (MA) acids and some of their derivatives, with a special emphasis on cell apoptosis and angiogenesis.

Photodynamic therapy (PDT) uses non-toxic dyes called photosensitizers (PS) to absorb light of visible or near-infrared wavelengths at non-thermal power densities that (in the presence of oxygen) combine together to produce reactive oxygen species (ROS). The main ROS formed are singlet oxygen and hydroxyl radicals that can both have cytotoxic effects. PDT has two separate mechanisms of specificity due to specific accumulation in the tumor coupled with spatially confined illumination. The first-generation PS were porphyrins, but due to the need for long-wavelength activation to improve tissue penetration, second- generation chlorins (far red) and bacteriochlorins (BC) (near infrared [NIR]) have been investigated. This review covers quantitative structure-function relationship with charge and lipophilicity, the effect the central metal atom has on determining the photochemical mechanism, the effect that electron withdrawing di-cyano groups have on preventing photobleaching, the improvement in activity found when micellar nanocarriers are employed, and the relative superiority of mono-substitution over symmetrical di- substitution. Finally, the necessity for long-wavelength (730 nm) activation is underlined by looking at PDT of pigmented melanoma in vitro and in a mouse model of melanoma.

Platinum (Pt)-based pharmaceutical drugs are among the most active agents utilized for the therapy of cancer. Carboplatin, cisplatin and oxaliplatin are three members of the platinum anticancer drug family approved by Food and Drug Administration (FDA). Despite gaining enormous success, the extensive application and efficacy of these drugs are often impeded by toxic side effects, their susceptibility to acquired drug resistance, and limited activity against many human cancers. These compounds are known to induce the apoptosis of tumor cells by binding to nuclear DNA, forming a variety of structural adducts to trigger cellular responses. To better understand the anticancer treatment with Pt-based chemotherapeutics, pharmaceutical formulations in perfect quality are required and the behavior of the drugs must be studied at therapeutically relevant levels by separation and detection of the intact drug and its individual biotransformation species in clinical samples. In this review, Pt-based drugs are introduced and the detection methods of Ptbased adduct with DNA and protein have been discussed.