Mini reviews in medicinal chemistry最新文献

Indole, a ubiquitous structural motif in bioactive compounds, has played a pivotal role in drug discovery. Among indole derivatives, indole-3-carboxaldehyde (I3A) has emerged as a particularly promising scaffold for the development of therapeutic agents. This review delves into the recent advancements in the chemical modification of I3A and its derivatives, highlighting their potential applications in various therapeutic areas. I3A derivatives have demonstrated a wide range of biological activities, including anti-inflammatory, anti-leishmanial, anti-cancer, anti-bacterial, antifungal, and anti-HIV properties. The structural modifications introduced to the I3A scaffold, such as substitutions on the indole ring (alkylation/arylation/halogenation), variations in the aldehyde group via condensation (Aldol/Claisen/Knoevenagel), and molecular hybridization with other reputable bioactive compounds like coumarins, chalcones, triazoles, and thiophenes, contribute to these activities. Beyond its therapeutic potential, I3A has also found applications as a ligand for Schiff base synthesis, a polymer, and a chromophore. This review provides a comprehensive overview of the latest research on I3A and its derivatives, focusing on the key reactions, modification pathways, reaction conditions, yields, and associated therapeutic activities. By understanding these advancements, researchers can gain valuable insights into the potential applications and future directions for I3A-based drug discovery.

Heterocyclic compounds are increasingly used in medicinal chemistry because they are the main components of many biological processes and materials. Benzimidazole remains the core center of the heterocyclic chemical group, with essential traits such as six-five-member connected rings and two nitrogen atoms at the 1,3 position in a six-membered benzene and five-membered imidazole- fused ring system. Molecules with benzimidazole derivatives serve important functions as therapeutic agents and have shown excellent results in clinical and biological research. In this comprehensive review, we summarize marketed medications that include the benzimidazole moiety. Here, we discuss two topics: PPIs and H₁ receptor antagonists. Benzimidazole derivatives are important in all fields because they have the same isostructural pharmacophore as that of naturally occurring active biomolecules. While PPIs and H1 receptor antagonists are generally safe in the short term, accumulating data suggest that their long-term use may pose concerns. This systematic review aimed to assess global PPI use in the general population. This will help researchers, medicinal chemists, and pharmaceutical scientists to create breakthrough benzimidazole-based drugs. This review can help identify novel lead compounds and optimize existing benzimidazole derivatives to improve medicinal efficacy. Benzimidazole has attracted significant interest because of its high bioavailability, stability, and biological efficiency. This page reveals and discusses typical synthesis processes for marketed pharmaceuticals in the benzimidazole class of scaffolds, MOA, and therapeutic uses.

In recent years, there has been a growing emphasis on the "back-to-nature" movement, which has brought biopolymers derived from natural sources into the spotlight. These biopolymers are gaining attention for their versatile surface-active properties, anti-adhesive capabilities, excellent biocompatibility, non-toxicity, biodegradability, and antimicrobial effectiveness against a wide range of oral microorganisms, including both bacteria and fungi. Researchers have been actively modifying these eco-friendly, nature-based biopolymers to enhance their interaction with surrounding cells and tissues, improving their performance in vivo. This has led to innovative applications in areas such as surface coatings, controlled drug delivery, tissue repair, and dental implant devices. These advancements hold the potential to pave the way for the development of novel drug delivery systems with enhanced therapeutic properties, ultimately supporting the creation of innovative formulations for clinical use. This review aims to provide an up-to-date overview of recent developments, explore potential future directions, and highlight the promising applications of nature-derived biopolymers in oral healthcare.

Globally, one of the most prevalent cancers is colorectal cancer (CRC). Chemotherapy and surgery are two common conventional CRC therapies that are frequently ineffective and have serious adverse effects. Thus, there is a need for complementary and different therapeutic approaches. The use of microbial metabolites to trigger epigenetic alterations as a way of preventing CRC is one newly emerging field of inquiry. Small chemicals called microbial metabolites, which are made by microbes and capable of altering host cell behaviour, are created. Recent research has demonstrated that these metabolites can lead to epigenetic modifications such as histone modifications, DNA methylation, and non-coding RNA regulation, which can control gene expression and affect cellular behaviour. This review highlights the current knowledge on the epigenetic modification for cancer treatment, immunomodulatory and anti-carcinogenic attributes of microbial metabolites, gut epigenetic targeting system, and the role of dietary fibre and gut microbiota in cancer treatment. It also focuses on short-chain fatty acids, especially butyrates (which are generated by microbes), and their cancer treatment perspective, challenges, and limitations, as well as state-of-the-art research on microbial metabolites-induced epigenetic changes for CRC inhibition. In conclusion, the present work highlights the potential of microbial metabolites-induced epigenetic modifications as a novel therapeutic strategy for CRC suppression and guides future research directions in this dynamic field.

A significant contributor to cancer-related death, pancreatic cancer (PC) has a terrible prognosis in general that has not altered over many years. Currently, it is extremely difficult to prevent disease or discover it early enough to initiate treatment. PC is a challenging malignancy to treat, and several major impediments significantly impact the effectiveness of its treatment. These obstacles primarily include chemoresistance, drug toxicity, and limited drug bioavailability. Phytochemicals can be used as an alternative to chemotherapeutic drugs, or they can augment the anticancer properties of the chemotherapeutic agents. Nimbolide (NL) is a prominent limonoid compound found in Azadirachta indica, and has garnered substantial attention as a phytochemical with anticancer potential. It has powerful antiproliferative effects on a variety of cancer cell lines and is effective as a chemotherapeutic in preclinical studies. The primary modes of action of NL include suppression of metastasis and angiogenesis, activation of apoptosis, anti-proliferation, and control of enzymes that metabolize carcinogens. Despite numerous pharmacodynamic (PD) investigations, NL is still in the early stages of the drug development process because no comprehensive pharmacokinetic studies or long-term toxicity studies. Preclinical and toxicological assessments should be conducted to establish an appropriate dosage range, ensuring the safety of NL for its application in initial human clinical trials. This review endeavors to provide a comprehensive summary of the current developmental stage of NL along with nanoparticles as a principal candidate for therapeutic purposes in PC.

Depression is a debilitating mental illness that has a significant impact on an individual's psychological, social, and physical life. Multiple factors, such as genetic factors and abnormalities in neurotransmitter levels, contribute to the development of depression. Monoamine oxidase inhibitors, tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRIs), serotoninnoradrenaline reuptake inhibitors, and atypical and new-generation antidepressants are well-known drug classes. SSRIs are the commonly prescribed antidepressant medications in the clinic. Genetic variations impacting serotonergic activity in people can influence susceptibility to diseases and response to antidepressant therapy. Gene polymorphisms related to 5-hydroxytryptamine (5-HT) signaling and subtypes of 5-HT receptors may play a role in the development of depression and the response to antidepressants. SSRIs binding to 5-HT reuptake transporters help relieve depression symptoms. Research has been conducted to identify a biomarker for detecting depressive disorders to identify new treatment targets and maybe offer novel therapy approaches. The pharmacological potentials of the piperazine-based compounds led researchers to design new piperazine derivatives and to examine their pharmacological activities. Structure-activity relationships indicated that the first aspect is the flexibility in the molecules, where a linker of typically a 2-4 carbon chain joins two aromatic sides, one of which is attached to a piperazine/phenylpiperazine/benzyl piperazine moiety. Newly investigated compounds having a piperazine core show a superior antidepressant effect compared to SSRIs in vitro/in vivo.

Ferroptosis is a novel type of programmed cell death that relies on the build-up of intracellular iron and leads to an increase in toxic lipid peroxides. Glutathione Peroxidase 4 (GPX4) is a crucial regulator of ferroptosis that uses glutathione as a cofactor to detoxify cellular lipid peroxidation. Targeting GPX4 in cancer could be a promising strategy to induce ferroptosis and kill drugresistant cancers effectively. Currently, research on GPX4 inhibitors is of increasing interest in the field of anti-tumor agents. Many reviews have summarized the regulation and ferroptosis induction of GPX4 in human cancer and disease. However, insufficient attention has been paid to GPX4 inhibitors. This article outlines the molecular structures and development prospects of GPX4 inhibitors as novel anticancer agents.

Pyridazinones are classical molecules that occupy an important place in heterocyclic chemistry, and since their discovery, they have been widely developed. The introduction of new functional groups into pyridazinone structures has enabled the synthesis of a large diversity of compounds. The pharmacological and agrochemical importance of pyridazinone derivatives has aroused the interest of chemists and directed their research toward the synthesis of new compounds with the aim of improving their biological effectiveness. In this review, we have compiled and discussed the different synthetic routes, reactivity, and pharmacological and agrochemical applications of the pyridazinone ring.

Carbamate has been extensively used as a scaffold in the recent era of drug discovery and is a common structural motif of many approved drugs. The carbamate moiety's unique amide-ester hybrid (-O-CO-NH-) feature offers the designing of specific drug-target interactions. Despite the discovery of numerous carbamate derivatives that act on the endocannabinoid system (ECS), the development of clinically effective carbamates remains a challenge. In this review, we highlight the therapeutic potential of carbamate inhibitors of endocannabinoid degrading enzymes as a breakthrough in discovering neurotherapeutic drugs. We discuss the design strategies and medicinal chemistry aspects involved in developing carbamate-based molecular architectures that modulate the endocannabinoid signaling pathway by interfering with fatty acid amide hydrolase (FAAH), monoacylglycerol lipase (MAGL), and α/β-Hydrolase domain-containing 6 (ABHD6). Additionally, we highlight the dual activity profile of carbamates against FAAH and MAGL, FAAH and cholinesterase, and FAAH and TRPV1 channels. Furthermore, we illustrate the pharmacophores of O-functionalized carbamates and N-cyclic carbamates that are crucial for FAAH and MAGL inhibitory activities, respectively.

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 minireview discusses the chemical synthesis and characterization of SPGG, along with its pharmacological effects derived from modulating the SGAG-protein interface.