Mini Reviews in Medicinal Chemistry - Current Issue

Taxol is a compound with a rigid, tetracyclic structure of diterpene, which is characterized by significant antitumor properties. Firstly, Taxol has been isolated by extraction from the bark of the yew tree. However, the low level of availability obligated the researchers' world to uncover alternative techniques of Taxol obtainment. In the last few years, many synthetic and semi-synthetic methodologies have been elaborated. Nowadays, many novel biotechnological approaches using cell suspension cultures and biotransformation are initiated and expanded. These processes are very beneficial. The reason is that both the final product and the yield of the process have high levels. Such approaches are very distinctive and they help achieve significant quantities of natural compounds, which often exist in small amounts in plants. Moreover, a very important aspect of Taxol development is nanotechnology. The use of this method has many benefits - the retention time is protracted and the concentration of a drug in tumor tissue is raised. This is due to the specific targeting of nanomolecules. What is essential for patients is that systemic side effects are reduced and the healthy biological systems and tissues do not damage. Also, the paper presents new directions with the application of Artificial Intelligence methods.

Every year, new concepts are created for obtaining Taxol and developing methods to significantly increase its bioavailability.

Sodium‐Glucose Co‐transporter‐1/2 (SGLT1/2) inhibitors (also called glifozins) are a class of glucose‐decreasing drugs in adults with Type 2 Diabetes (T2D). SGLT2 inhibitors diminish sodium and glucose reabsorption in the renal proximal convoluted tubule. Recent clinical trials have revealed that SGLT2 inhibitors might be beneficial for treating diseases other than diabetes, including chronic renal disease and Heart Failure (HF). Currently, SGLT2 inhibitors are recommended not only for the glycemic management of T2D but also for cardiovascular protection. SGLT2 inhibitors have become one of the foundational drugs for HF with reduced Ejection Fraction (HFrEF) treatment and the first medications with proven prognostic benefit in HF with preserved Ejection Fraction (HFpEF). At present, 11 SGLT1/2 inhibitors have been approved for clinical use in different countries. Beyond their anti-hyperglycemic effect, these inhibitors have shown clear cardio- and nephroprotective properties. A growing body of research studies suggests that SGLT1/2 inhibitors may provide potential clinical benefits in metabolic as well as oncological, hematological, and neurological disorders.

Sulfated glycosaminoglycans (SGAGs), such as heparin, are complex linear polysaccharides attached to core proteins via covalent bonds to form proteoglycans. SGAGs are crucial in assembling extracellular matrix, the regulation of cell signaling and cell behavior, hemostasis, development, and various diseases, including thrombosis, cancer, infectious diseases, and neurodegenerative disorders, through their binding with diverse proteins. Despite the abundant SGAG-protein interactions provided by nature, the development of small SGAG-like molecules remains underexplored. However, sulfonated penta-galloyl glucose (SPGG) represents a promising, easily synthesized, small-molecule mimetic of SGAGs, capable of harnessing these interactions. This mini-review discusses the chemical synthesis and characterization of SPGG, along with its pharmacological effects derived from modulating the SGAG-protein interface.

Glioblastoma (GBM) is the most prevalent and deadly primary brain tumor. The current treatment for GBM includes adjuvant chemotherapy with temozolomide (TMZ), radiation therapy, and surgical tumor excision. There is still an issue because 50% of patients with GBM who get TMZ have low survival rates due to TMZ resistance. The activation of several DNA repair mechanisms, such as Base Excision Repair (BER), DNA Mismatch Repair (MMR), and O-6-Methylguanine-DNA Methyltransferase (MGMT), is the main mechanism via which TMZ resistance develops. The zinc-finger DNA-binding enzyme poly (ADP-ribose) polymerase-1 (PARP1), which is activated by binding to DNA breaks, affects the activation of the MGMT, BER, and MMR pathway deficiency, which results in TMZ resistance in GBM. PARP inhibitors have been studied recently as sensitizing medications to increase TMZ potency. The first member of the PARP inhibitor family to be identified was Olaparib. It inhibits PARP1 and PARP2, which causes apoptosis in cancer cells and DNA strand break. Olaparib is currently investigated as a radio- and/or chemo-sensitizer in addition to being used as a single agent because it may increase the cytotoxic effects of other treatments. This review addresses Olaparib and its significance in treating TMZ resistance in GBM.

The statistical data related to cancer in recent years has shown a great increase in the number of cases and is likely to further increase in the future. Even after seeking thorough knowledge on the aetiology of cancer and related disorders and attempting to cure it by various methods like gene therapy, T cell therapy, chemotherapy, surgery, hormone therapy, and photodynamic therapy, there has always been disappointment concerning the survival rate. Hence, there is still a great urge for the discovery of novel drugs for the treatment of cancer. Chemotherapy being one of the widely used methods, several drug entities possessing anticancer properties are already in the market but none of them is known to show good efficacy which necessitates researchers to design newer drugs for the treatment of cancer. The urge to synthesize novel anticancer entities directed researchers towards molecular hybridization as one of the novel methods for designing newer drugs. Literature reveals wide research carried out on quinolin-2-one hybrids, possessing anticancer properties through different mechanisms. Tipifarnib and Dovitinib are quinolin-2-one hybrids used to treat cancer, possessing imidazole and benzimidazole heterocyclic rings. Different heterocyclic scaffolds such as pyrone, pyrrole, pyrimidine, pyridine, thiazole, and pyrazole in combination with heterocyclic quinolin-2-one have shown high potential to become lead for newer anticancer agents with better and wider therapeutic properties and lesser side effects. The current review presents information on the different quinolin-2-one hybrids and their effect on different cancer cell lines. It also imparts knowledge of the structural requirements for designing novel anticancer agents.

Green tea (GT) is rich in phyto-active compounds such as epigallocatechin gallate (EGCG), epigallocatechin (EGC), epicatechin gallate (ECG), epicatechin (EC), catechin, and tannic acid, which exhibit synergistic effects when combined. Preclinical studies demonstrate that GT and its compounds can reduce reactive oxygen species (ROS), enhance antioxidant capacity, and alleviate aging-related issues such as memory impairments, cognitive decline, and shortened lifespan. Clinical trials corroborate the efficacy of topical GT formulations in improving skin tone, texture, and elasticity and reducing wrinkles. The present manuscript summarizes the recent update on the anti-aging potential of GT and its possible mechanisms. The literature survey suggests that GT consumption is linked to improved cognition, reduced depression levels, and activation of pathways in model organisms like C. elegans. Additionally, tea polyphenols enhance fibroblast mitophagy, boost hippocampal synaptic plasticity in rodents, and mitigate age-related cognitive decline. Moreover, EGCG exhibits anti-aging properties by reducing TNF-induced MMP-1 expression, suppressing ERK signaling, and inhibiting MEK and Src phosphorylation in human dermal fibroblasts. In the context of skin permeation and deposition, optimized transfersomal formulation (TF) incorporating EGCG and hyaluronic acid (HA) demonstrates significantly increased skin permeation and deposition of EGCG compared to plain EGCG. Furthermore, EGCG protects cardiomyocytes via the PPARγ pathway and combats age-related muscle loss through miRNA-486-5p regulation, AKT activation, and FoxO1a-mediated expression of MuRF1 and Atrogin-1. In conclusion, the regular consumption of GT holds promise for promoting physical and mental health, delaying brain and skin aging, and improving overall health by enhancing total antioxidant capacity.