Letters in Drug Design & Discovery - Volume 21, Issue 13, 2024

IntroductionCharcot Marie Tooth Disease-2 is a debilitating neurogenetic disorder that adversely affects peripheral neurons by disrupting mitochondrial activity. Mutated mitofusin-2 (MFN) is the main culprit behind disruptive mitochondrial function and is considered a therapeutic target in identifying drugs for treating this disease. This disease has no therapeutic medication except for supportive care.ObjectiveThe objecti Read More

The investigation is devoted to the assessment of the potential antimicrobial use of new chalcogen-functionalized thiazolo[2,3-b]quinazolin-5-ones, halides and trihalides of thiazolo[3,2-a]quinazolin-10-ium and tribromides thiazino[3,2-a]quinazolin-11-ium. The compounds under study were obtained by electrophilic intramolecular heterocyclization. A high bactericidal and fungicidal effect against some gram-positive and gra Read More

BackgroundNovel antibiotics are needed to stem the rise of antimicrobial resistance. N-Methyl-2-phenylmaleimide (NMP) compounds previously synthesised by our research group are structural analogues of 2,3,5-substituted perhydropyrrolo[3,4-d]isoxazole-4,6-diones found by others to have antibacterial activity.ObjectivesThis study aims to explain the significance of NMPs and their antibacterial activity. The antibacterial activi Read More

The increase in multi-drug resistant (MDR) pathogens and the decline in the number of new antibiotics in the production pipeline pose a serious threat to our ability to treat infectious diseases. In this new landscape, once treatable diseases are now potentially life-threatening. This impending danger requires that urgent attention should be given to developing alternative strategies for combating MDR bacteria. A novel alternati Read More

An energetic desire to reduce the undesirable effects brought on by synthetic heterocyclic substances and to combat antimicrobial resistance has led to an increase in curiosity in using natural antimicrobial agents derived from plants, such as phenolics, catechol, pyrogallol, essential oils, L-chicoric acid, caffeic acid, catechins, coumarin, proanthocyanidins, 4-thiazolidinone, and alkaloids. The usage of naturally occurring hete Read More

Allograft rejection is one of the main problems that must be overcome. Evidence suggests a role of the local renin-angiotensin system (RAS) in the progress of chronic allograft injury. Angiotensin II, generated by the renin-angiotensin system, is well-known as a major regulator molecule to control the blood pressure and fluid system. Evidence suggests that this bioactive molecule and its receptor increase the risk of tissue inj Read More

Nanotechnology has made great strides in developing targeted drug delivery systems over the past few decades. These systems have garnered attention for their unique biological properties and ability to deliver drugs in a stable and sustainable manner. Despite these advances, there are still concerns about quality, efficacy, and safety. Many fabrication techniques still need to be refined to address the complex structures a Read More

ObjectiveInfectious keratitis is a pernicious disease that affects the anterior segment of the eye and is one the leading causes of blindness worldwide. This disease may cause severe visual impairment or permanent vision damage if left untreated.DiscussionNo doubt there are many conventional drug delivery systems to treat ocular keratitis, yet it is the fifth leading cause of blindness globally. This is the result of the e Read More

BackgroundAcquired Immunodeficiency Syndrome (AIDS) is one of most prevalent infectious diseases in the world, and HIV-1 protease (PR) is a vital target of drug design. Nowadays, three-dimensional quantitative structure-activity relationships (3D-QSAR) are applied to help design new protease inhibitions (PIs).ObjectiveThe primary objective of this study is to apply the 3D-QSAR study to a series of 42 derivatives of Daru Read More

BackgroundModern pharmacological research indicated that Camellia nitidissima (CAM) had significant anti-tumor activity, but the investigation of its mechanism was still lacking.ObjectiveThe multi-component, multi-target and multi-pathway mechanism of CAM against tumor was investigated based on network pharmacology and molecular docking.MethodsThe active ingredients and targets of CAM were selected through a lite Read More

BackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer-related deaths. Banzhilian (BZL) and Baihuasheshecao (BHSSC) are classical Chinese herbs used in tumor therapy. However, the underlying mechanisms of BZL-BHSSC in treating PDAC have not been identified. Combining network pharmacology with single-cell RNA sequencing (scRNA-seq), this study systematically explored the potenti Read More

BackgroundThe lead compounds isolated from medicinal plants constitute a matrix for research and discovery of new drugs using in silico study and molecular docking.ObjectiveThis work explores the in silico study and the molecular docking of two rare phytochemicals, namely Microphynolide A (1) and Microphynolide B (2), isolated from the Saharan medicinal plant Thymelaea microphylla (Thymelaeaceae famil Read More

BackgroundThe prevalence of cancer in developing nations is a significant issue of concern. As a result of diverse global influences, this condition has surpassed coronary ailments to become the foremost cause of mortality. The role of PKM2 (Muscle Pyruvate Kinase 2) has garnered significant interest in the quest for agents in cancer progression. Flavonoids exhibit promise as a framework for the advancement of chemotherap Read More

Backgroundβ-Glucosidase has a variety of biological functions. A structural model for a potential β-glucosidase inhibitor has been proposed in the studies.ObjectiveA series f new diaryl derivatives linked through benzimidazole have been randomly and rationally designed, synthesized, and evaluated for their inhibitory activities against β-glucosidase (almond). The proposed structural model provides a new strategy for the d Read More

BackgroundThe co-infection of HIV and abdominal TB poses a worldwide danger to humanity. This is because there are more strains of bacteria that are resistant to many classes of currently available medications. According to current findings, repurposing existing available medications will result in more effective functioning than using newly designed medications.ObjectiveBased on this fact, we hypothesised that the PI coul Read More

BackgroundThe activated oncogenic Notch signalling is an emerging target to treat cancer progression and recurrence. Synthetic inhibitors of Notch receptors are in pre-clinical studies. However, the overexpression of Notch signalling molecules at the gene level needs to be regulated to control cancer progression.ObjectiveWe propose that this can be achieved by gene-regulatory drugs in combination with natural phytoc Read More

BackgroundNowadays, inflammation is recognized as the underlying cause of a number of diseases, but NSAIDs are the first drug of choice, having several side effects. Additionally, excessive cellular oxidative stress is often considered a major contributor to pathophysiological conditions, the development of cancer, and other diseases. Antimicrobial resistance is a global concern, hence, there is a critical need for the develop Read More

BackgroundFruits like berries are known not only for their taste and nutritional value but also for the potential health benefits of their bioactive components. Stilbenes, a group of phenolic metabolites found in berries, demonstrate significant pharmacological activities. Its derivatives also have been investigated for their biological functions, including as anticancer agents. Bcl-2 antiapoptotic proteins are highly involved in re Read More

BackgroundNon-alcoholic fatty liver disease (NAFLD) is considered the most common liver disease. Shugan Jiangzhi Decoction (SJD), a traditional Chinese medicine (TCM) formula which consists of six Chinese herbs, has been used for treating hyperlipidemia, obesity, and fatty liver in Guangdong Provincial Hospital of Traditional Chinese Medicine for over twenty years.ObjectiveThis study aims to elucidate the chemical Read More

BackgroundThe clinical applications of platinum-based anticancer drugs are largely compromised by side effects and drug resistance. Therefore, novel platinum-based anticancer drugs with improved injected or oral therapeutic index and low resistance need to be developed.ObjectiveThis study aimed at the synthesis and anticancer activity testing of Pt(IV) prodrugs containing α-furancarboxylate as an axial ligand. This wou Read More