Medicinal Chemistry

The catalytic activity of DNA-dependent protein kinase (DNA-PK) is central to its ability to repair lethal DNAdouble strand breaks (DSBs). This includes repair of DSB lesions following therapeutic treatment of cancer cells or resulting from oxidative stress or oncogene-induced transcription. As a tactic to induce tumour chemo- and radio-sensitisation, numerous attempts have been made to identify small molecule inhibitors of DNA-PK activity. This review examines the structures of known reversible and irreversible inhibitors, including those based upon chromen-4-one, arylmorpholine, and benzaldehyde scaffolds. VX-984 and M3814 are recent examples of DNA-PK catalytic inhibitors that have progressed into clinical development, the results from which should help to further advance our understanding of whether this approach represents a promising therapeutic strategy for the treatment of cancer.

Simple coumarins and analogues are large class of compounds that have attracted their interest for a long time due to their biological activities. They have shown to be useful as anti-tumoural, anti-HIV agents and as CNS active compounds. Furthermore, they have been reported to have multiple biological activities (anti-coagulant, anti-inflammatory), although all these properties have not been evaluated systematically. In addition, their enzyme inhibition properties, antimicrobial and antioxidant activities are other foremost topics in this field of research. A new series of thiazolidinedione derivatives were synthesized by reacting with coumarin moiety and studied for their antibacterial and antifungal activities. The synthesis of compounds (6a-9c) was achieved through the versatile and efficient synthetic route that involved reaction of thiazolidinedione with appropriately α-bromo ketone or α-bromo oxime derivatives (2a, 5c). The structures of these compounds were established by means of IR, 1H-NMR, 13C-NMR Mass and elemental analysis.

Placenta is endocrine organ that regulate biological function of several maternal tissues and fetal organs by specific mechanisms of cell-to-cell cooperation, which is realized via exosomes’ secretion. Exosomes delivery some molecules, i.e., active proteins, pro-coagulants, growth factors, lipids, enzymes, micro-RNAs to target cells and induce autocrine / paracrine effects on vasculature and trophoblast. Interestingly, circulating number of exosomes derived from placenta cells in healthy pregnancies increases in 50-100 fold times to healthy volunteers and they may be detected in several biological fluids across all gestation age starting with 6 weeks of gestation. Moreover, pregnancies at risk of preeclampsia exhibit extremely increased levels of total exosomes and placental cell-derived-exosomes in blood when compared with woman at risk free of preeclampsia. Taking into consideration this fact, measure of circulating number of placental cell-derived-exosomes could be an individual probe for personification of a risk of life-threatening event across pregnancy. The short communication is depicted the role of placental cell-derived-exosomes as biomarker of preeclampsia in asymptomatic pregnancies.

Contraception plays a pivotal role in birth control and family planning and thus affects millions of women not only in the U.S. but also world-wide. Efforts are made in the U.S. to reduce the percentage of unwanted pregnancies, i.e., 49%, which compares unfavorably with Western Europe's percentage of 34% [1,2]. Despite a vast and steadily-increasing literature on the issues of family planning and birth control, several questions are still awaiting clarification, especially with regard to medicinal chemistry, i.e., effects of chemical substances on human endocrinology. The following analysis aims at identifying problem areas in contemporary research and draws attention to flawed data in scholarly publications.