European Journal of Medicinal Chemistry Reports最新文献

Based on the chemotherapeutic success of cisplatin, carboplatin and oxaliplatin as anticancer drugs, and silver sulfadiazine (AgSDZ) as an antibacterial drug, exploration of the anticancer and antibacterial potential of new metal complexes has received increasing attention during the last three decades. Saccharin (sacH) is a well-known worldwide artificial sweetener. Its deprotonated form (sac) is a polyfunctional ligand, coordinating to different metals due to the presence of hard and soft donor sites (see comment below). In the last two decades, a large number of mixed-ligand metal complexes containing sac and tsac ligands have been synthesized and in some cases, they have demonstrated better in vitro and in vivo biological activities than approved standard drugs. This review describes the design, anticancer and antimicrobial activity screening of metal complexes of sac and its thio derivative (tsac) as prospective drug candidates. The metal sac complexes herein are categorized according to the ancillary ligands present in the complexes, and their anticancer and antimicrobial activities are discussed in detail. The main molecular targets and cellular pathways involved in the mechanism of action of the metal complexes were also explored. The growing field demonstrates promising in vitro and in vivo results with a significant interest for future research in medicinal inorganic chemistry.

Traditional drug delivery systems have fallen short in addressing the complex medical and therapeutic needs of patients, necessitating the development of more efficient alternatives. These novel systems aim to enhance treatment efficacy while minimizing adverse effects. Advances in drug delivery technology have significantly improved drug loading and release, administration methods, pharmacological profiles, and the creation of innovative drug formulations. This review delves into current methodologies employed in silica-based targeted drug delivery systems. After examining the structure and properties of various silicas, we focus on mesoporous nanoparticles for targeted drug delivery, exploring existing approaches and addressing critical concerns such as silica safety and biodegradability. Additionally, this review provides a brief overview of bioassays, cell tracking, and tumor-specific targeting strategies.

In the present paper, pyrazole and pyrazoline derivatives of β-ionone were synthesized. The protocol involved intramolecular oxidative C–H amination of hydrazone to yield corresponding pyrazole in moderate to good yields. Another methodology comprising of condensation of hydrazine hydrochloride with β-ionone in methanol leading to pyrazoline and its oxidative dehydrogenation using hypervalent iodine reagent to synthesize pyrazole is also achieved. One pot methodology for synthesis of pyrazole is also developed by refluxing the hydrazine hydrochloride with β-ionone in acetic acid. The structures of the synthesized compounds were elucidated using ¹H NMR, ¹³C NMR, FTIR and mass spectrometry. All the pyrazole and pyrazoline derivatives were subjected to bovine serum albumin assay for in-vitro anti-inflammatory activity and all the compounds exhibited good to excellent activity. Compounds containing bromo and sulfonamide group exhibited inhibition rates of 87.36 % and 85.82 %, respectively, at a concentration of 0.5 mg/mL, surpassing the efficacy of the standard drug celecoxib (81.67 %). Further, cytotoxicity of the compounds was also evaluated against VERO cell line and all the compounds exhibited the cytotoxic values almost similar to the standard. Molecular docking was performed to study binding affinity of the potent compounds i. e bromo bearing pyrazole and sulfonamide bearing pyrazoline into the crystal structure of COX-II enzyme (PDB ID: 3LN1) at celecoxib binding site to determine the binding energy and interactions.

Acquired immune deficiency syndrome (AIDS) diseases despite the efficacy of anti-HIV therapy, remain one of the human's most serious problems. Hence, the introduction of novel anti-HIV agents as first-line therapy is still required. HIV integrase lacking human enzyme homologous is an interesting target for developing new anti-HIV drugs. Following our attempts to describe active integrase inhibitor structures, here a series of novel 4-Hydroxy-5-pyrrolinone-3-carbohydrazides as HIV integrase inhibitor agents were identified. Biological results showed that all compounds could inhibit integrase strand transfer reaction and also exhibited anti-HIV activity in a cell-based assay. The interaction between integrase and designed compounds was investigated using molecular docking and molecular dynamics simulations.

Type 2 diabetes is a common condition that causes the level of glucose in the blood to become too high and α-glucosidase inhibitors are therapeutic agents in managing type 2 diabetes. In the present study, we report a new series of 3-aceto(benzo)hydrazide-1,2,4-triazine analogs as potential therapeutic agents against type 2 diabetes. In the in vitro evaluations, most compounds showed much stronger α-glucosidase inhibitory activity than the standard drug acarbose. Especially, compound 2A, (N'-(5,6-diphenyl-1,2,4-triazin-3-yl)-4-methoxybenzohydrazide) as the most active compound showed IC₅₀ = 12.0 μM which is 60 folds more potent than acarbose. In addition, the MTT test using the three cell lines HCT-116, MDA-MB-231, and A549 showed that the target compounds have low cytotoxic effects with IC₅₀ values in the range of 60–280 μM, therefore they can be considered as safe compounds. Molecular docking studies predicted that the strong inhibitory activity of 2A is related to the interactions generated by the three residues Asp282, Trp481, and Asp616 with the triazine core and hydrazide motif in the active site of the enzyme. The significant inhibitory effect of 2A against α-glucosidase was also confirmed in vivo, where the compound showed equivalent activity to the standard drug acarbose on reducing blood glucose in the tested mice. In conclusion, this study introduces compound 2A as a new lead compound with favorable cytotoxicity, strong α-glucosidase inhibitory activity and in vivo hypoglycemic effect, for future investigation in the treatment of diabetes mellitus.

In this study, 56 isoxazole derivatives were synthesized and their antitumor activity against 9 cancer cells, such as BXPC-3, MiaPaCa-2, PANC-1, MCF-7, HCT-116, HepG2, NCI-H460, A549 and B16 was detected. The results of pharmacological experiments indicated that most compounds exhibit good cytotoxicity against nine cancer cells. Among them, compound 14–3 has an IC₅₀ of 2.4 μM for colon cancer cells HCT-116, which shows the best effect and is better than the broad-spectrum drug 5-Fluorouracil (5-Fu) for the treatment of colon cancer. In addition, 14–3 induces apoptosis and leads to cell cycle arrest in the G2/M phase. Cytotoxicity tests on human normal hepatocytes LO2 also demonstrates that 14–3 is less toxic than 5-Fu with no obvious toxicity. These results suggest that 14–3 is a potential candidate for the development of anti-tumor drugs.

Background

Cosmetic microneedling has emerged as a popular minimally invasive technique. This systematic review employs the SWOT (Strengths, Weaknesses, Opportunities, Threats) analysis framework to comprehensively evaluate the current landscape of cosmetic microneedles.

Method

The review incorporates a rigorous examination of peer-reviewed articles, the number of publications from the year 2008–2023, clinical trials, market products and devices available, and patents related to cosmetic microneedles. The selection criteria include relevance to SWOT analysis, publication quality, and recency. A systematic and transparent methodology is employed to ensure the inclusion of the most pertinent and reliable evidence available.

Conclusion

Microneedle systems in cosmetic applications reveal a dynamic landscape marked by strengths such as precise drug delivery and self-administration potential. However, these cutting-edge mechanisms face challenges, including concerns about skin damage and regulatory complexities. Opportunities lie in the targeted delivery capabilities across diverse cosmetic treatments, from hair growth to scar reduction and anti-wrinkle therapy. Incorporating artificial intelligence (AI) and machine learning into microneedling procedures has the potential to transform numerous aspects of cosmetic treatment. The insights gained from this analysis are relevant for practitioners, researchers, and industry professionals, guiding future research directions, technological advancements, and strategic decision-making in the cosmetic microneedling domain.

The scientific community has long been interested in capsaicin, and the extensive hunt for AChE and BChE enzyme inhibitors is still ongoing. In this investigation analogs of capsaicin, such as the pharmaceutical nonivamide, which is preferred in clinical settings for the topical treatment of pain, were explored in the search for appropriate inhibitors. Thus, to test their inhibitory effect on AChE and BChE, we synthesized a short series of derivatives derived from vanillylamide. Consequently, it was discovered that compounds 12, 34, and 35, which have K_i values in the sub-micromolar concentration range, are especially effective inhibitors. Compound 12 demonstrated dual mixed-type (competitive/uncompetitive) inhibitory activity for both enzymes; compound 34 showed selective mixed-type inhibitory activity for AChE, and compound 35 was found to have selective uncompetitive activity for AChE.

Conventional pharmaceutical interventions often entail considerable financial burdens and are frequently associated with a plethora of adverse effects. Consequently, an escalating number of individuals are turning to herbal remedies to ameliorate the symptoms of various ailments. Nonetheless, a significant proportion of medicinal plants remain underexplored. Smyrnium olusatrum L., a biennial herbaceous plant belonging to the Apiaceae family, colloquially known as Alexanders or Wild celery, has been traditionally employed in the treatment of colds and hemorrhages. Pharmacological investigations have highlighted the abundant presence of flavonoids and ascorbic acid in this plant. However, predominant research focus has been directed towards its essential oils. Intriguingly, a myriad of compounds derived from Smyrnium olusatrum L. exhibit noteworthy antioxidant, anticancer, anti-inflammatory, antimicrobial, and antiparasitic activities. The primary objective of this review is to elucidate structural variabilities in compounds across distinct plant parts and geographical origins of Smyrnium olusatrum L. Additionally, this review seeks to systematically compile data pertaining to the diverse biological effects observed both in vitro and in vivo, thereby elucidating the underlying mechanisms governing these effects.

Metronidazole (MTZ) is a vital antimicrobial agent widely used in the treatment of various infections. However, its limited bioavailability and associated side effects necessitate the development of efficient drug delivery systems to enhance therapeutic efficacy and minimize adverse reactions. The field of nanotechnology and nanomaterials presents promising solutions for delivering MTZ, leveraging their unique properties to overcome these challenges. This comprehensive review explores a variety of nanomaterial-based approaches for MTZ delivery, emphasizing the benefits such as improved drug stability, targeted release, and enhanced bioavailability. Various nanocarrier systems, including polymeric nanoparticles, lipid-based nanocarriers, and inorganic nanoparticles, are evaluated for their potential in MTZ delivery applications. The review underscores strategies aimed at reducing MTZ's side effects through controlled release and targeted delivery, with nanocarriers facilitating sustained drug release to minimize fluctuations in drug concentrations and potentially mitigate adverse reactions linked to MTZ administration. Furthermore, innovative combination therapies involving MTZ and other drugs are investigated for their ability to enhance therapeutic outcomes and combat drug resistance. Co-delivery systems show promise in synergistically targeting infections while reducing overall dosage and associated side effects. By summarizing the latest advancements in MTZ delivery, this review provides valuable insights into the potential of nanotechnology-based strategies for optimizing MTZ therapy. These approaches have the potential to transform drug delivery, offering safer and more effective treatments for infectious diseases, and improving patient outcomes by reducing adverse effects.