Synthesis and Biological Evaluation of Novel Uracil Derivatives as Thymidylate Synthase Inhibitors.

Cell division is driven by nucleic acid metabolism, and thymidylate synthase (TYMS) catalyzes a rate-limiting step in nucleotide synthesis. As a result, thymidylate synthase has emerged as a critical target in chemotherapy. 5-Fluorouracil (5-FU) is currently being used to treat a wide range of cancers, including breast, pancreatic, head and neck, colorectal, ovarian, and gastric cancers The objective of this study was to establish a new methodology for the low-cost, one-pot synthesis of uracil derivatives (UD-1 to UD-5) and to evaluate their therapeutic potential in BC cells. One-pot organic synthesis processes using a single solvent were used for the synthesis of drug analogues of Uracil. Integrated bioinformatics using GEPIA2, UALCAN, and KM plotter were utilized to study the expression pattern and prognostic significance of TYMS, the key target gene of 5-fluorouracil in breast cancer patients. Cell viability, cell proliferation, and colony formation assays were used as in vitro methods to validate the in silico lead obtained. BC patients showed high levels of thymidylate synthase, and high expression of thymidylate synthase was found associated with poor prognosis. In silico studies indicated that synthesized uracil derivatives have a high affinity for thymidylate synthase. Notably, the uracil derivatives dramatically inhibited the proliferation and colonization potential of BC cells in vitro. In conclusion, our study identified novel uracil derivatives as promising therapeutic options for breast cancer patients expressing the augmented levels of thymidylate synthase.

Chemokines in triple-negative breast cancer heterogeneity: New challenges for clinical implications.

Tumor heterogeneity is a hallmark of cancer and one of the primary causes of resistance to therapies. Triple-negative breast cancer (TNBC), which accounts for 15-20% of all breast cancers and is the most aggressive subtype, is very diverse, connected to metastatic potential and response to therapy. It is a very diverse disease at the molecular, pathologic, and clinical levels. TNBC is substantially more likely to recur and has a worse overall survival rate following diagnosis than other breast cancer subtypes. Chemokines, low molecular weight proteins that stimulate chemotaxis, have been shown to control the cues responsible for TNBC heterogeneity. In this review, we have focused on tumor heterogeneity and the role of chemokines in modulating tumor heterogeneity, since this is the most critical issue in treating TNBC. Additionally, we examined numerous cues mediated by chemokine networks that contribute to the heterogeneity of TNBC. Recent developments in our knowledge of the chemokine networks that regulate TNBC heterogeneity may pave the way for developing effective therapeutic modalities for effective treatment of TNBC.

Imidazoles as potential anticancer agents.

Cancer is a black spot on the face of humanity in this era of science and technology. Presently, several classes of anticancer drugs are available in the market, but issues such as toxicity, low efficacy and solubility have decreased the overall therapeutic indices. Thus, the search for new promising anticancer agents continues, and the battle against cancer is far from over. Imidazole is an aromatic diazole and alkaloid with anticancer properties. There is considerable interest among scientists in developing imidazoles as safe alternatives to anticancer chemotherapy. The present article describes the structural, chemical, and biological features of imidazoles. Several classes of imidazoles as anticancer agents based on their mode of action have been critically discussed. A careful observation has been made into pharmacologically active imidazoles with better or equal therapeutic effects compared to well-known imidazole-based anticancer drugs, which are available on the market. A brief discussion of the toxicities of imidazoles has been made. Finally, the current challenges and future perspectives of imidazole based anticancer drug development are conferred.

Advances in Nanocarriers for Anticancer Drugs Delivery.

Cancer is the most dangerous disease to haunt the mankind in the world today. Generally, the overall cancer mortality rates are similar in both the sexes. The reasons for most of these deaths are inefficacy and failure of the current methods of treatments or the unavailability of treatment options. The researchers of the world are actively integrating nanotechnology of treating of various cancers. The development of smart nanocarriers is one of the most important innovations in this direction. The nanocarriers of the different materials are being developed to improve the efficacy of current treatments. The present article describes the role of nanotechnology in cancer treatment emphasizing cancer nanotherapy, nanocarriers for drug delivery, types and the mechanisms of the nanocarriers. Besides, the efforts are made to discuss the recent advances in the nanocarriers, current challenges and the future prospective.

Heterocyclic Scaffolds: Centrality in Anticancer Drug Development.

Cancer has been cursed for human beings for long time. Millions people lost their lives due to cancer. Despite of the several anticancer drugs available, cancer cannot be cured; especially at the late stages without showing any side effect. Heterocyclic compounds exhibit exciting medicinal properties including anticancer. Some market selling heterocyclic anticancer drugs include 5-flourouracil, methortrexate, doxorubicin, daunorubicin, etc. Besides, some natural products such as vinblastine and vincristine are also used as anticancer drugs. Overall, heterocyclic moeities have always been core parts in the expansion of anticancer drugs. This article describes the importance of heterocyclic nuclei in the development of anticancer drugs. Besides, the attempts have been made to discuss both naturally occurring and synthetic heterocyclic compounds as anticancer agents. In addition, some market selling anticancer heterocyclic compounds have been described. Moreover, the efforts have been made to discuss the mechanisms of actions and recent advances in heterocyclic compounds as anticancer agents. The current challenges and future prospectives of heterocyclic compounds have also been discussed. Finally, the suggestions for syntheses of effective, selective, fast and human friendly anticancer agents are discussed into the different sections.