Mini Reviews in Medicinal Chemistry - Volume 21, Issue 7, 2021

The inherited mutations and underexpression of BRCA1 in sporadic breast cancers resulting in the loss or functional inactivation of BRCA1 may contribute to a high risk of breast cancer. Recent researchers have identified small molecules (BRCA1 mimetics) that fit into a BRCA1 binding pocket within Estrogen Receptor alpha (ERα), mimic the ability of BRCA1 to inhibit ERα activity, and overcome antiestrogen resistance. Studies indicate that most of the BRCA1 breast cancer cases are associated with p53 mutations. It indicates that there is a potential connection between BRCA1 and p53. Most p53 mutations are missense point mutations that occur in the DNA-binding domain. Structural studies have demonstrated that mutant p53 core domain misfolding, especially p53-R175H, is reversible. Mutant p53 reactivation with a new class of zinc metallochaperones (ZMC) restores WT p53 structure and functions by restoring Zn²⁺ to Zn²⁺ deficient mutant p53. Considering the role of WT BRCA1 and reactivation of p53 in tumor cells, our hypothesis is to target both tumor suppressor proteins by a novel biomolecule (ZMC). Since both proteins are present in the same cell and are functionally inactive, this state may be a novel efficacious therapeutic regime for breast cancer therapy. In addition, we propose to use Albumin Nanovector (ANV) formulation for target drug release.

Background: The mammalian target of rapamycin (mTOR), protein tyrosine phosphatase 1b (PTP1B) and dipeptidase 4 (DPP4) signaling pathways regulate eukaryotic cell proliferation and metabolism. Previous researches described different transduction mechanisms in the progression of cancer and diabetes. Methodology: We reviewed recent advances in the signal transduction pathways of mTOR, PTP1B and DPP4 regulation and determined the crosstalk and common pathway in diabetes and cancer. Results: We showed that according to numerous past studies, the proteins participate in the signaling networks for both diseases. Conclusion: There are common pathways and specific proteins involved in diabetes and cancer. This article demonstrates and explains the potential mechanisms of association and future prospects for targeting these proteins in pharmacological studies.

The search for mitochondria-targeted drugs has dramatically risen over the last decade. Mitochondria are essential organelles serving not only as a powerhouse of the cell but also as a key player in cell proliferation and cell death. Their central role in the energetic metabolism, calcium homeostasis and apoptosis makes them an intriguing field of interest for cancer pharmacology. In cancer cells, many mitochondrial signaling and metabolic pathways are altered. These changes contribute to cancer development and progression. Due to changes in mitochondrial metabolism and changes in membrane potential, cancer cells are more susceptible to mitochondria-targeted therapy. The loss of functional mitochondria leads to the arrest of cancer progression and/or a cancer cell death. Identification of mitochondrial changes specific for tumor growth and progression, rational development of new mitochondria-targeted drugs and research on delivery agents led to the advance of this promising area. This review will highlight the current findings in mitochondrial biology, which are important for cancer initiation, progression and resistance, and discuss approaches of cancer pharmacology with a special focus on the anti-cancer drugs referred to as ‘mitocans’.

Parasite Plasmodium falciparum is continuously giving a challenge to human beings by changing itself against most of the antimalarial drugs and its consequences can be seen in the form of a huge number of deaths each year especially in the poor and developing country. Due to its drug resistance ability, new drugs are regularly needed to kill the organism. Many new drugs have been developed based on different mechanisms. One of the potential mechanisms is to hamper protein synthesis by blocking the gene expression. S-Adenosyl-L-homocysteine (SAH) hydrolase is a NAD+ dependent tetrameric enzyme, which is responsible for the reversible hydrolysis of AdoHcy to adenosine and L-homocysteine, has been recognized as a new target for antimalarial agents since the parasite has a specific SAH hydrolase. The inhibition of SAH hydrolase causes the intracellular accumulation of S-Adenosyl-L-homocysteine, elevating the ratio of SAH to S-adenosylmethionine (SAM) and inhibiting SAM-dependent methyltransferase that catalyzes methylation of the capped structure at the 5′-terminus of mRNA, and other methylation reaction which is essential for parasite proliferation. In other words, S-Adenosyl-Lhomocysteine hydrolase regulates methyltransferase reactions. In this way, SAH hydrolase inhibitors can be used for the treatment of different diseases like malaria, cancer, viral infection, etc. by ultimately stopping the synthesis of protein. Many antiviral drugs have been synthesized and marketed which are based on the inhibition of SAH hydrolase. This review summarises the development of SAH inhibitors developed over the last 20 years and their potentiality for the treatment of malaria.

Background: Cancer has become the second leading cause of death worldwide. Despite of the availability of significant number of anticancer agents, cancer is still incurable especially at the last stages. Remarkable targets for anticancer research and drug discovery are heterocyclic compounds, and among them, superior effect has been shown by the nitrogen containing compounds than non-nitrogen containing compounds. Nicotinic acid, a nitrogen containing moiety and its derivatives have gained an immense importance in the development of anticancer drugs owing to the wide variety of biological properties displayed by them. Objective: The objective of this review is to provide researchers the information about various synthetic approaches used for the synthesis of anticancer drugs of nicotinic acid from 2001 onwards and to reveal their application and importance in the treatment of this dreadful disease. Conclusion: As indicated by this review, considerable work has been done in terms of synthesis and investigation of anticancer potential of nicotinamide derivatives. The information provided in this article may be of great value for the researchers seeking to develop efficient anticancer drugs.

Background: Breast cancer is the most frequent cancer in women. Green tea has been studied for breast cancer chemopreventive and possibly chemotherapeutic effects due to its high content in polyphenolic compounds, including epigallocatechin-3-gallate (EGCG). Method: This review is based on literature research that included papers registered on the Medline® database. The research was conducted through PubMed, applying the following query: “EGCG”AND "breast cancer”. The result was a total of 88 articles in which this review stands on. Results: In vitro, EGCG shows antioxidant or pro-oxidant properties, depending on the concentration and exposure time. EGCG blocks cell cycle progression and modulates signaling pathways that affect cell proliferation and differentiation. EGCG also induces apoptosis, negatively modulates different steps involved in metastasis, and targets angiogenesis by inhibiting VEGF transcription. In vivo investigations have shown that oral administration of EGCG results in the reduction of tumor growth and in antimetastatic and antiangiogenic effects in animal xenograft and allograft models. Discussion: Much remains unknown about the molecular mechanisms involved in the protective effects of EGCG on mammary carcinogenesis. In addition, more studies in vivo are necessary to determine the potential toxicity of EGCG at higher doses and to elucidate its interactions with other drugs. Conclusion: A protective effect of EGCG has been shown in different experimental models and under different experimental conditions, suggesting clinical implications of EGCG for breast cancer prevention and therapy. The data presented in this review support the importance of further investigations.

In modern dentistry, nanomaterials have strengthened their foothold among tissue engineering strategies for treating bone and dental defects due to a variety of reasons, including trauma and tumors. Besides their finest physiochemical features, the biomimetic characteristics of nanomaterials promote cell growth and stimulate tissue regeneration. The single units of these chemical substances are small-sized particles, usually between 1 to 100 nm, in an unbound state. This unbound state allows particles to constitute aggregates with one or more external dimensions and provide a high surface area. Nanomaterials have brought advances in regenerative dentistry from the laboratory to clinical practice. They are particularly used for creating novel biomimetic nanostructures for cell regeneration, targeted treatment, diagnostics, imaging, and the production of dental materials. In regenerative dentistry, nanostructured matrices and scaffolds help control cell differentiation better. Nanomaterials recapitulate the natural dental architecture and structure and form functional tissues better compared to the conventional autologous and allogenic tissues or alloplastic materials. The reason is that novel nanostructures provide an improved platform for supporting and regulating cell proliferation, differentiation, and migration. In restorative dentistry, nanomaterials are widely used in constructing nanocomposite resins, bonding agents, endodontic sealants, coating materials, and bioceramics. They are also used for making daily dental hygiene products such as mouth rinses. The present article classifies nanostructures and nanocarriers in addition to reviewing their design and applications for bone and dental regeneration.