Mini reviews in medicinal chemistry最新文献

Organic compounds containing azines, di-imines, or bis-Schiff-bases have two azomethine (-CH=N-) functional groups associated with a bridging component. These constituents have attracted attention from a diversity of disciplines, comprising coordination, medicinal, agriculture chemistry, and organic synthesis, because of their comprehensive chemical reactivity and nature. This study determines common synthetic approaches and various biological and pharmacological activities of several substituted bis-Schiff byproducts. The usefulness of bis-Schiff bases in synthetic chemistry and their potential as inhibitors of a number of enzymes have attracted research attention. We have examined different biological activities and common synthetic methods used to make bis- Schiff bases that have been published in the literature. A systematic search of the literature has been performed, and studies fitting the prearranged inclusion standards have been inspected. This review can open up new potentials for upcoming research in this area and advance our information on bis- Schiff bases.

After cisplatin discovery in anticancer treatment, many metals have been studied as potential antitumor agents, especially group IXB elements, such as rhodium, iridium, palladium, and their complexes. The design of polymetallic complexes containing different metal centers with diverse pharmacological characteristics has raised considerable interest in the field of drug development research. This approach aims to exploit the synergistic effect of distinct metal cations, which could contribute to enhancing biological activity. The basic rationale is that the combination of two or more metal ions with the same or different cytotoxic profiles and modes of action may significantly modify the anticancer potential of the resulting complexes, thus enlarging the biological targets and improving the biodistribution properties compared to mononuclear fragments. Among the reported multinuclear anticancer complexes, rhodium-based compounds have attracted considerable attention despite their relatively limited history. The current article presents the results obtained in the field of rhodium complexes, highlighting the recent advances of polynuclear homometallic rhodium compounds as promising antineoplastic candidates. While widespread studies have focused on mononuclear rhodium complexes, the potential of polynuclear Rh-based compounds with structural and functional diversity remains rather understudied. This low interest is most likely due to the typical kinetic inertness and chemical stability of most rhodium complex compounds. These complexes have garnered considerable attention due to their enhanced cytotoxic effects, intracellular distribution, and selectivity, thereby holding promising prospects for the further development of multifunctional drug candidates with desired activity. Recent developments of polynuclear rhodium-based antitumor agents have been summarized in the current review.

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.

Influenza viruses are major human pathogens that cause widespread respiratory infections, affecting millions of people globally and contributing to significant morbidity and mortality. Several currently available anti-influenza drugs are facing increasing levels of viral resistance. Therefore, the discovery of therapeutics targeting novel mechanisms of action is becoming increasingly important. A key viral protein involved in the infection process is the envelope glycoprotein Hemagglutinin (HA), which facilitates both host cell receptor binding and membrane fusion, two essential steps required for viral entry and replication. Due to its central role in the early stages of infection, HA has emerged as a highly promising target for antiviral drug development. Many smallmolecule HA inhibitors have been identified with potential anti-influenza activity by stabilizing the HA structure and preventing its conformational change during the membrane fusion process. This review presents a detailed chemical evaluation of these HA-targeting compounds based on studies reported in the literature, highlighting their core chemical scaffolds and structural features. The antiviral efficacy of these compounds is discussed based on in vitro and in vivo data, along with insights into their mechanisms of action. A comprehensive literature search was conducted, and studies meeting the predefined inclusion criteria were thoroughly reviewed. By focusing on the chemical structure of these inhibitors, this review provides information for the rational design of new therapeutic agents aimed at preventing or limiting influenza virus infections.

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.

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.

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.

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.

Parkinson's Disease (PD) is the most common neurodegenerative disorder after Alzheimer's Disease and is clinically expressed by movement disorders, such as tremor, bradykinesia, and rigidity. It occurs mainly in the extrapyramidal system of the brain and is characterized by dopaminergic neuron degeneration. L-DOPA, dopaminergic agonists, anticholinergic drugs, and MAO-B inhibitors are currently used as therapeutic agents against PD, however, they have only symptomatic efficacy, mainly due to the complex pathophysiology of the disease. This review summarizes the main aspects of PD pathology, as well as, discusses the most important biochemical dysfunctions during PD, and presents novel multi-targeting compounds, which have been tested for their activity against various targets related to PD. This review selects various research articles from main databases concerning multi-targeting compounds against PD. Molecules targeting more than one biochemical pathway involved in PD, expected to be more effective than the current treatment options, are discussed. A great number of research groups have designed novel compounds following the multi-targeting drug approach. They include structures combining antioxidant, antiinflammatory, and metal-chelating properties. These compounds could be proven useful for effective multi-targeted PD treatment. Multi-targeting drugs could be a useful tool for the design of effective antiparkinson agents. Their efficacy towards various targets implicated in PD could be the key to the radical treatment of this neurodegenerative disorder.

Sustainable chemistry and nature-friendly protocols are not only luxury but has become essential requirement for the modern society as it progresses towards a more responsible future. To match the current needs of the community, industries and in particular chemical industry is looking for novel and cheap strategies that have less adverse effects on the environment. Heterocyclic compounds are one particular motif, which is prevalent in nature. It is found in a wide range of synthetic and natural compounds, both established and in development as potent therapeutic candidates. According to the US retail market in 2014-2015, heterocyclic moieties constitute the basic skeletons for 80% of marketed pharmaceuticals. However, majority of the synthetic methodologies still uses classical approaches with toxic solvents, stoichiometric reagents, reactions with less atom economy etc. Thus, there is an urgent need for green, sustainable alternatives of the classical reactions. In recent years, an array of diverse approaches and technologies have been discovered by the scientific community to address the issue of eco-friendly manufacture of various pharmaceutically and medicinally important heterocyclic molecules. In this context, the current review will summarize various reported green pathways to the heterocyclic architecture, particularly O, N, and S-heterocyclic compounds. The methods highlighted in this article includes reaction in environment friendly nonconventional media, solvent-free approaches, heterogeneous catalysis, organocatalysis, electrochemical reactions, microwave-mediated reactions, ultrasound-based reactions, enzymatic reactions, biocatalysis, and others.