Letters in Drug Design & Discovery - Volume 21, Issue 17, 2024

This perspective focuses on the hyper-permeable vasculature, contributing to the passive accumulation of drugs or NP-drug combinations through the paracellular and/or transcellular pathways. This unique, cardinal, pathological feature of the vasculature in solid tumors is a major determinant for the entry of anti-cancer macromolecules, with longer drug retention, attributable to imperfections in the lymphatic drainage system. Read More

Parkinson's disease (PD) is an age-related progressive neurodegenerative condition characterized by dopaminergic neuronal loss in the brain's substantia nigra pars compacta (SNpc). Growing evidence suggests that apoptosis, neuroinflammation, mitochondrial dysfunction, and oxidative stress are important factors in the pathogenesis of Parkinson's disease. Isoquercetin is a natural flavanol compound possessing anti-apo Read More

Pyrazolone has a wide range of biological activities, including anti-inflammatory, antibacterial, antifungal, antimicrobial, anti-tubercular, anti-oxidant, anti-helminthic, and anticancer effects. Due to their various clinical practice and research activities, they have a wide range of applications and prospects. They continue to be the subject of many research and analytical studies to learn more about their medicinal chemistry. I Read More

Herbal and dietary supplements are products that add more nutritional value to the diet. The use of these products has increased worldwide and has become widespread. Recently, the food products market has witnessed significant advancements in improving the health and well-being of individuals with increased nutritional requirements or in preventing related diseases and conditions. Overall, dietary supplements posses Read More

Inflammation, follicular epidermal hyperproliferation, and Propionibacterium acnes (P. acnes) are the primary causes of acne vulgaris, a prevalent skin condition that affects millions of young adults and adolescents. This intricate pathophysiology leads to various acne symptoms, such as whiteheads and blackheads, inflammatory nodules, and scarring. Among the many traditional allopathic acne therapies that often have Read More

BackgroundWD repeat structural domain 5 (WDR5), which plays an important role in various biological functions through epigenetic regulation, is aberrantly expressed in human cancers, and is an effective target for the discovery of anticancer drugs.MethodsIn this paper, QSAR modeling analysis, including comparative molecular field (CoMFA) and comparative molecular similarity index analysis field (CoMSIA), was first per Read More

BackgroundThe adenovirus vector has been widely studied for vaccines and gene therapies. During the production of the adenovirus vector, a high virus titer is desired to obtain enough virus. The adenovirus vector has been widely studied for the vaccinations and gene therapies, where a high virus titer is desired to obtain sufficient quantities of the virus. For an adenovirus vector-based vaccine, suppression of antigen expressio Read More

BackgroundDrug resistance poses a threat to global health given the disturbing rate at which microbiological illnesses are rising and the widespread use of antibiotics. While naturally occurring antibiotics reduce the likelihood of bacterial resistance, recognized drugs can develop the same properties when structurally modified. Metronidazole has been targeted to achieve this feat.ObjectiveThe purpose of this work is to ena Read More

IntroductionNovel sulfonamides containing pyrazole and 1,2,3-triazole were synthesized, and their inhibitory effects on six common pathogenic bacteria and COX-2 were investigated to screen new sulfonamides antimicrobial agents and COX-2 inhibitors with better effects.MethodsThe compounds with bacteriostatic effect were screened by using the ring of inhibition method and MTT chromogenic method, and the mec Read More

BackgroundTemperature-sensitive (thermo-sensitive) formulations are a novel drug delivery dosage form that shows bio-inspired behavior in various applications. The structure and properties of a thermosensitive polymer are critical in designing an intelligent biometric polymer that contains lipopeptide biosurfactants.ObjectiveIn this study, thermo-sensitive hydrogels with lipopeptide biosurfactants as a potential woun Read More

IntroductionHIV-1, the primary causative agent of AIDS, remains a formidable and lethal virus globally, claiming the lives of millions over the past four decades since its discovery. Recent research has underscored the potential of HIV-1 protease as a therapeutic target, offering a promising strategy for inhibiting viral replication within the body.MethodsIn light of this, we have curated an extensive database comprising 193 de Read More

BackgroundRheumatoid arthritis (RA) is a self-inflammatory disease with increasing global morbidity and high disability. The Chinese herbal medicine Rhododendron molle G. Dons has been conventionally used to control RA without side effects for hundreds of years, but its effect and mechanism for anti-RA are still unclear.ObjectiveThe objective of this study is to study the potential effect and mechanism of R. molle ag Read More

BackgroundDexamethasone (DEX), delivered through newly developed self-nanoemulsifying drug delivery systems, which is administered to rabbit eyes, has been presented. The instrumental parameters of the multiple LC-MS/MS methods in the literature are modified according to rabbit vitreous liquid and current laboratory conditions.MethodsQuick optimization of the chromatographic and mass spectrometric parameter Read More

BackgroundRheum khorasanicum is a medicinal plant that belongs to the Polygonaceae family. This family is well-known for its anticancer activities.ObjectiveDue to the limited studies on the anticancer activity of R. khorasanicum, the present study aimed to evaluate the apoptotic effect of this medicinal plant on MDA-MB-231 cells as a model for an aggressive triple-negative breast cancer that has a lower treatment optio Read More

BackgroundOxidative stress plays a key role in the development of a wide range of diseases, including diabetes and cancer. Recent studies reported that the derivatives of triazole compounds have a potent antioxidant activity. Therefore, this study was designed to investigate the hepatoprotective effect of a novel newly synthesized 5-mercapto-1,2,4-triazole based on nalidixic acid [1-ethyl-3-(5-mercapto-4-(p-tolyl)- Read More

ObjectiveThis study aimed to assess the combinational antidiabetic effect of catechin and metformin in streptozotocin (STZ)-induced diabetic rats.MethodsWistar rats were chosen and divided into five groups (n=6). STZ at the dose of 55 mg/kg was used intraperitoneally for the induction of diabetes. The combination of catechin (CTN) and metformin (MET) was administered to diabetic rats. The changes in fasting blood sugar Read More

BackgroundInflammation is an immunological reaction against an aggressor agent. NLRP3 inflammasome is a component of the immune system, which, when excessively activated, results in several inflammatory diseases, making it an attractive target for discovering anti-inflammatory drugs. Computer-Aided Drug Design (CADD) techniques are powerful tools used to search for new drugs in less time and financial cost. Recentl Read More

BackgroundLead-like drugs, which present molecular weight (MW) < 300 Da, occupy an important space in the pharmaceutical area. Most of these small molecules have ring systems, which are important for their physicochemical properties and biological activity. Previous studies have evaluated ring systems in historic drugs or drug candidates in clinical trials.ObjectiveThe purpose of this work was to analyze ring syste Read More

BackgroundOptimal glycemic control is crucial in type 2 diabetes treatment, with α-glucosidase inhibitors emerging as promising candidates. Avenanthramides, compounds found in oats, exhibit therapeutic potential, but their efficacy as α-glucosidase inhibitors requires thorough evaluation.ObjectiveThis study investigates the potential of avenanthramides and their derivatives as inhibitors of α-glucosidase for the t Read More

IntroductionBerberine is an important isoquinoline alkaloid that has various pharmacological properties. The comparison of the binding pocket similarity of berberine is regarded as the starting point for deciphering various activities.MethodsEight berberine protein crystals were clustered and studied by molecular dynamics (MD) simulations to investigate common features of berberine binding pockets.ResultsRoot Mean Sq Read More

BackgroundPostoperative adhesions commonly occur after abdominal surgery and can lead to significant complications. There is increasing evidence that targeting the renin-angiotensin system (RAS) can reduce inflammation and fibrosis. This study investigates the therapeutic potential of enalapril, an RAS inhibitor, in a rat model of postsurgical adhesion band formation.MethodsA total of 12 male albino Wistar rats receiv Read More

BackgroundIn the field of pharmaceutical chemistry, the anti-cancer activity of such compounds received great attention. For both medicinal and industrial studies. Xanthene derivatives are important class of compounds that have had many applications and this enhanced their uses in recent years. Xanthene and its derivatives are extensively used scaffolds in drug designing and the development of novel anti-cancer agents du Read More

BackgroundN-benzoyl-N'-naphthylthiourea (BNTU) is a thiourea-derived compound that is predicted to have anti-breast cancer activity. However, their physicochemical properties, ADMET, and receptor-specific targets for their anti-breast cancer activity have not been reported.ObjectiveThis study aimed to predict the physicochemical properties, ADMET, and anti-breast cancer activity of BNTU and its derivatives by in silico ap Read More

BackgroundIt has been reported that PKCθ plays an important role in the immune response by regulating the cellular activity of T cells and, thus, the production of immune factors such as IL-2.PKCθ protein is mainly expressed in T lymphocytes but not much in other cells and has a very good specificity. Therefore, it is very meaningful to use PKCθ protein as a novel target for immunosuppression. PKCθ is a valuable target that Read More

BackgroundIn recent years, in silico computational approaches have tremendously guided computational medicinal chemists and research scientists to analyze protein structures, kinetics, functions, and molecular interactions of the administered drugs.ObjectiveThis study aimed to identify a novel inhibitor against SARS-CoV-2 using human CD26 and modeled spike protein through suitable in silico approaches.Method Read More

BackgroundAHR and its signaling pathways are promising therapeutic targets for psoriasis. Recent studies in traditional Chinese medicine have confirmed that Indirubin acts as an efficient ligand of AHR, inhibiting the inflammatory response. Clarifying its mechanism of action remains essential.ObjectiveThis study uses bioinformatics to predict Indirubin’s potential molecular mechanism in treating psoriasis and validate t Read More

BackgroundIntra-abdominal adhesions are a commonly occurring postoperative complication following abdominopelvic surgery. Peritoneal adhesion formation can lead to infertility, chronic pelvic pain, and intestinal obstruction. The anti-inflammatory and anti-oxidant activities of Ganoderma lucidum Karst (G. lucidum) and Ziziphus jujuba Mill (Z. jujuba) have been reported. Here, we have explored the therapeutic Read More

Background and ObjectivesSalmonella typhimurium is a foodborne pathogen that is a major concern for global health. Flagellin (FliC) is an essential protein in Salmonella typhimurium for both motility and virulence and is a key component of flagella. Hence, focusing on FliC protein is a promising strategy for developing new anti-Salmonella agents. Colchicum luteum, a medicinal plant, shows promising antimicrobial properties. Thu Read More

BackgroundSevere acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 Mpro) has been shown to be an effective target for inhibiting novel coronaviruses, which can be used as a crucial breakthrough for developing drugs to treat the coronavirus disease 2019 (COVID-19).MethodsTo design novel SARS-CoV-2 Mpro inhibitors, we conducted 3D-QSAR, molecular docking, and molecular dynamics (MD) sim Read More

BackgroundThe synthesis of metal-based nanoparticles through conventional methods involves harsh conditions, high costs, and severe environmental threats. To overcome these issues, researchers are nowadays focusing on eco-friendly and low-cost methods for the synthesis of nanoparticles. Finally, several plant-mediated synthesis techniques have been developed, which have various advantages, such as low-c Read More

PurposeThis study mainly made use of network pharmacology and molecular docking to analyze the therapeutic mechanism of pulmonary arterial hypertension (PAH) by the traditional medicinal food plant Lycium barbarum L. in Ningxia.MethodsThe related targets and active compounds in PAH and Lycium barbarum L. were analyzed through the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platf Read More

BackgroundPistacia atlantica Desf., also known as Atlantic pistachio or Mt. Atlas mastic tree, has been used in traditional medicine for its anti-inflammatory properties, helping to reduce inflammation in conditions like arthritis. Additionally, the tree's resin possesses antioxidant properties that can help protect against oxidative stress.The anti-arthritic efficacy of Pistacia atlantica oleo-gum resin extract (PAG) remains unvali Read More

ObjectivesIntra-abdominal adhesions are the most frequently occurring postoperative complication following abdominopelvic surgery. Peritoneal adhesion formation can lead to infertility, chronic pelvic pain, and intestinal obstruction. Several studies have shown the potential role of metformin in reducing inflammation. Here, we explored the therapeutic potency of Metformin against postsurgical adhesion band formation.Metho Read More

BackgroundCancer represents the major health problem faced by the population of the world, remaining one of the main causes of death. Hence, the development of new targeted antitumor drugs with high efficacy and lower toxicity is still needed.ObjectiveAs a continuation of our work to discover new molecules with cytotoxic properties, two heterocyclic scaffolds, namely indolizine, and indazole, were combined in the sam Read More

BackgroundDespite advancements in treatment modalities, the search for new cytotoxic agents remains vital in the fight against cancer. This ongoing effort aims to introduce novel molecules that serve as potent cytotoxic agents while minimizing adverse effects.ObjectiveThe objective of the study is to design, synthesize, and evaluate Fmoc-L-Lysine Carboxamides for cytotoxic activities.MethodsThe title compounds 4a-l w Read More

ObjectiveThe aim of this study was to explore the mechanisms of Trigonella foenum-graecum L. (T. foenum-graecum) in the treatment of type 2 diabetes mellitus (T2DM).MethodsThe TCSMP database was utilized to obtain the constituents and targets of T. foenum-graecum. The OMIM database was used at GeneCard to acquire T2DM targets. The STRING database was used to plot the PPI network. KEGG and GO analys Read More

BackgroundImatinib, a frontline targeted-therapeutic agent for patients with chronic myelogenous leukemia (CML), was a synthetic tyrosine kinase inhibitor approved by the US Food and Drug Administration.ObjectiveTo expand the structural diversity of Bcr-Abl inhibitors, we synthesized nine novel imatinib analogues (1a-1i) and evaluated their cytostatic effects against human cancer cell lines in vitro.MethodsImatinib and its a Read More

ObjectiveApproximately 10%-40% of the global population is affected by allergic rhinitis, and Lycium barbarum has a long history of dual use as a herbal medicine and also as a food. This study utilized network pharmacology and molecular docking to explore the mechanism of action of Lycium barbarum in treating allergic rhinitis.MethodsWe screened active ingredients and potential action targets of Lycium barbarum using the Read More