Current Topics in Medicinal Chemistry - Volume 22, Issue 7, 2022

Cancer and cardiovascular diseases have become one of the leading causes of death worldwide. Therefore, early detection of these diseases and rapid intervention by medical staff remain a great challenge for clinicians and healthcare providers worldwide. Cancer and cardiovascular disease biomarkers are promising tools for early diagnosis before it becomes incurable at an advanced stage. They also contribute to monitoring the progress of therapy and surgical treatment. Indeed, sensors have shown great importance for detecting cancer and cardiovascular biomarkers. Sensors usually require a recognition element for the selective detection of targets. Molecularly imprinted polymer (MIP), as an artificial antibody, has been proposed as an alternative recognition element in sensing fields to overcome the main drawbacks of natural antibodies. With the high need for sensors providing results quicklyand making the early diagnosis of these diseases easier, MIP-based sensors are attracting considerable interest recently, which will undoubtedly be increased in the future due to the sustainability trend. The key aim of this review is to emphasize the recent applications of sensors based on MIP for the detection of cancer and cardiovascular biomarkers and to highlight the key advances related to MIP-based sensors. Furthermore, several key future trends about the applications of MIP-based sensors for detecting cardiovascular and cancer biomarkers are presented.

Human carbonic anhydrase (CA) IX is a tumor-associated protein since it is scarcely present in normal tissues but highly overexpressed in a large number of solid tumors, where it actively contributes to survival and metastatic spread of tumor cells. A variety of approaches and design strategies were reported that afford CA IX/XII specific inhibitors and avoid the compromising effects of isoforms-promiscuous compounds. CA IX inhibitors hybrids/conjugates have become an important scaffold to design therapeutic agents with both CA inhibition and anti-cancer effects. In this review, we firstly present an overview of the role of CA IX in hypoxic tumors physiopathology, then provide a comprehensive update on the rational design and synthesis of small molecule CA IX inhibitors discovered since 2019. Also, their structure-activity relationship analysis studies are covered. A brief description of applications for CA IX inhibition in other therapeutic areas is also provided.

Flavonoids are secondary metabolites of plants. In general#140;most flavonoids are combined with glucosides and have extremely complex molecular structures. In nature, these flavonoids have a variety of biological activities, such as anti-oxidation#140;anti-virus, anti-tumor, scavenging free radicals, etc.; however#140;due to poor solubility and stability of flavonoids#140;their bioavailability is limited. The drug design method is used to modify the structure of flavonoids to give them special properties. At present, flavonoids have shown broad application prospects in treating tumors, inhibiting proliferation, migration, invasion, angiogenesis, and multi-drug resistance of tumors and have become a research hotspot.

The oxadiazole core is considered a privileged moiety in many medicinal chemistry applications. The oxadiazole class includes 1,2,3-oxadiazole, 1,2,4-oxadiazole, 1,3,4-oxadiazole, and 1,2,5-oxadiazole. Compounds bearing an oxadiazole ring show a wide range of biological activities, such as anticancer, antibacterial, anti-inflammatory, anti-malarial, and insecticidal properties. Among oxadiazoles, the 1,3,4-oxadiazole has been the most widely explored moiety in medicinal chemistry research. This review is primarily focused on the anticancer, antibacterial, and anti-inflammatory activities of compounds containing 1,2,4-oxadiazole, 1,3,4-oxadiazole and 1,2,5-oxadiazole reported in the last five years.

In recent years, bromodomain-containing protein 4 (BRD4), a member of the bromodomain and extra terminal domain (BET) family, has been one of the most widely studied targets. BRD4 is a transcriptional regulation factor, which regulates cell transcription, marks mammalian biological mitosis, regulates cell cycle, and plays an important role in the biological process of cancer occurrence and development. It has been demonstrated that the imbalance or dysfunction of BRD4 expression leads to various types of cancers, including testicular gene nuclear protein melanoma, acute myeloid leukemia, colon cancer, breast cancer, liver cancer, and midline cancer. Therefore, inhibition of BRD4 has become a valuable approach in the treatment of these cancers. To date, there are numerous BRD4 inhibitors in preclinical development, some of which have entered human clinical trials. In this review, current progress in the development of privileged scaffolds designed as BRD4 inhibitors will be discussed by focusing on structure-activity relationship, selectivity, and mechanisms of action.