The discovery of tumor angiogenesis opened a new path in fighting cancer. The approval of different antiangiogenic agents, most targeting vascular endothelial growth factor (VEGF) signaling, has either increased the effectiveness of standard chemotherapy or even replaced it by offering better patient outcomes. However, an increasing number of preclinical and clinical observations have shown that the process of angiogenesis is far from clearly understood. Apart from targeting the VEGF pathway, novel strategies aim to influence other molecular factors that are involved in tumor angiogenesis. In addition, naturally occurring compounds seem to offer additional agents for influencing angiogenesis. The first concept of antiangiogenic therapy aimed to destroy tumor vessels, while it turned out that, paradoxically, antiangiogenic drugs normalized vasculature and as a result offered an improvement in chemotherapeutic delivery. In order to design an effective treatment schedule, methods for detecting the time window of normalization and biomarkers predicting patient response are needed. The initial idea that antiangiogenic therapy would be resistance-free failed to materialize and currently we still face the obstacle of resistance to antiangiogenic therapy.

Colchicine is a well-known compound with strong antiproliferative activity that has had limited use in chemotherapy because of its toxicity. In order to create more potent anticancer agents, a series of novel colchicine derivatives have been obtained by simultaneous modification at C7 (amides and sulfonamides) and at C10 (methylamino group) positions and characterized by spectroscopic methods. All the synthesized compounds have been tested in vitro to evaluate their cytotoxicity toward A549, MCF-7, LoVo, LoVo/DX and BALB/3T3 cell lines. Additionally, the activity of the studied compounds was investigated using computational methods involving molecular docking of the colchicine derivatives to β-tubulin. The majority of the obtained derivatives exhibited higher cytotoxicity than colchicine, doxorubicin or cisplatin against tested cancer cell lines. Furthermore, molecular modeling studies of the obtained compounds revealed their possible binding modes into the colchicine binding site of tubulin.

A series of 12 novel monosubstituted N-benzyl amides of salinomycin (SAL) was synthesized for the first time and characterized by NMR and FT-IR spectroscopic methods. Molecular structures of three salinomycin derivatives in the solid state were determined using single crystal X-ray method. All compounds obtained were screened for their antiproliferative activity against various human cancer cell lines as well as against the most problematic bacteria strains such as methicillin-resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis (MRSE), and Mycobacterium tuberculosis. Novel salinomycin derivatives exhibited potent anticancer activity against drug-resistant cell lines. Additionally, two N-benzyl amides of salinomycin revealed interesting antibacterial activity. The most active were N-benzyl amides of SAL substituted at -ortho position and the least anticancer active derivatives were those substituted at the -para position.