Current Topics in Medicinal Chemistry - Online First

Cancer is a multifaceted disease with high mortality rates, and current treatments face challenges such as chemoresistance and tumor adaptation. Since Virchow reported the first case of cancer-related chronic inflammation, numerous clinical and epidemiological studies have indicated that around 15-20% of malignant tumors are caused by inflammation. Cyclooxygenase-2 (COX-2), which is the key enzyme in inflammation, has been implicated in tumorigenesis through various mechanisms, including promoting angiogenesis, inhibiting apoptosis, and enhancing the invasiveness of cancer cells. Moreover, COX inhibitors have demonstrated a substantial reduction in death rates associated with esophageal and colon cancer. In this context, targeting COX-2 is an effective strategy for cancer prevention and treatment.

This review focuses on the analysis of studies conducted between 2014 and 2024, which evaluate the structure-activity relationship of molecules intended to exhibit cytotoxic activity through COX inhibition. The studies followed both classical and non-classical COX-2 selective drug design strategies. While some focused on the classical approach, utilizing diaryl heterocyclic structures, others explored non-classical designs with a cyclic central scaffold and a linear core. Additionally, several manuscripts employed well-known COX inhibitors, including licofelone, indomethacin, naproxen, tolfenamate, celecoxib, flumizole, and ketoprofen, as starting points for further derivatization and optimization. Cytotoxic activity was evaluated using various cell lines, including MCF-7, HCT-116, and A549, through assays such as MTT, CellTiter, and MTS. Additionally, studies examined the relationship between COX-2 inhibition and key cancer pathways, including apoptosis and the involvement of enzymes like HDAC, EGFR, and topoisomerase.

The majority of studies reported promising cytotoxic activity in COX-2 selective inhibitors. Compounds synthesized with diphenyl heterocyclic scaffolds exhibited enhanced COX-2 selectivity and anticancer efficacy. In particular, derivatives in studies 9, 16, and 24 demonstrated significant activity comparable to standard drugs like celecoxib and doxorubicin. However, only a few studies indicated a weak correlation between COX-2 inhibition and cytotoxicity, suggesting the need for further investigation into other cancer-related mechanisms.

This review highlights the potential of COX-2 selective inhibitors in anticancer drug development. The findings support the development of selective COX-2 inhibitors with diverse chemical structures as a promising strategy for cancer therapy.

Cardiovascular disorders develop the highest rates of mortality and morbidity worldwide, emphasizing the need for novel pharmacotherapies. The Chinese medicinal plant S. baicalensis has a number of major active components, one of which is called baicalin. According to emerging research, baicalin reduces chronic inflammation, immunological imbalance, lipid metabolism, apoptosis, and oxidative stress. Baicalin improves endothelial function and protects the cardiovascular system from oxidative stress-induced cell injury by scavenging free radicals and inhibiting xanthine oxidase. Therefore, it helps prevent CVD such as hypertension, atherosclerosis, and cardiac arrest. In this review, the therapeutic effects of baicalein are discussed in relation to both the prevention and management of cardiovascular diseases.

Healthy skin is essential for balanced health. Currently, skin diseases are considered a major global health issue, impacting individuals of all ages. Skin conditions can vary broadly, ranging from common issues like acne and eczema to more serious diseases such as psoriasis, melanoma, and other types of skin cancer. In recent years, computational methods have appeared as powerful tools for explaining the lurking mechanisms of skin diseases and the advancement of the discovery regarding updated therapeutics. This review spotlights the notable researches that have been performed in using computational approaches such as virtual screening, molecular modelling, and molecular dynamics simulations to discover potential treatments for dermatological conditions such as eczema, psoriasis, acne vulgaris, skin cancer, and tyrosinase-related disorders. Moreover, using in silico methods, researchers have explored the molecular interactions between cosmetic actives and skin targets, providing insights into the binding affinities, stability, and efficacy of these compounds. This computational exploration allows the identification of potential off-target effects and toxicity profiles, ensuring that only the most promising candidates proceed to clinical testing. In addition, the use of molecular dynamics simulations helps to understand conformational changes and interaction dynamics over time, further refining the selection of effective cosmetic actives. Overall, the integration of computational chemistry into dermo-cosmetic research has immense potential to accelerate the discovery and development of innovative treatments to improve skin health and address dermatological concerns.