designer drug

The supramolecular-based macrocyclic amphiphiles have fascinating attention and find extensive utilization in the pharmaceutical industry for efficient drug delivery. In this study, we designed and synthesized a new supramolecular amphiphilic macrocycle to serve as an efficient nanocarrier, achieved by treating 4-hydroxybenzaldehyde with 1-bromotetradecane. The derivatized product was subsequently treated with resorcinol to cyclize, resulting in the formation of a calix(4)-resorcinarene-based supramolecular amphiphilic macrocycle...

As a sort of fluorescent carbon nanomaterial with a particle size of less than 10 nm, carbon dots (CDs) have their own merits of good dispersibility in water, stable optical properties, strong chemical inertness, stable optical properties, and good biosecurity. These excellent peculiarities facilitated them like sensing, imaging, medicine, catalysis, and optoelectronics, making them a new star in the field of nanotechnology. In particular, the development of CDs in the fields of chemical probes, imaging, cancer therapy, antibacterial and drug delivery has become a hot topic in current research...

Deep learning is becoming increasingly relevant in drug discovery, from de novo design to protein structure prediction and synthesis planning. However, it is often challenged by the small data regimes typical of certain drug discovery tasks. In such scenarios, deep learning approaches-which are notoriously 'data-hungry'-might fail to live up to their promise. Developing novel approaches to leverage the power of deep learning in low-data scenarios is sparking great attention, and future developments are expected to propel the field further...

We consider a model of basic inner retinal connectivity where bipolar and amacrine cells interconnect and both cell types project onto ganglion cells, modulating their response output to the brain visual areas. We derive an analytical formula for the spatiotemporal response of retinal ganglion cells to stimuli, taking into account the effects of amacrine cells inhibition. This analysis reveals two important functional parameters of the network: (1) the intensity of the interactions between bipolar and amacrine cells and (2) the characteristic timescale of these responses...

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disease that imposes economic and societal burden. Biomarkers have played a crucial role in the recent approval of aducanumab and lecanemab as disease-modifying therapies which marked a significant milestone for the treatment of AD. The inclusion of biomarkers in AD trials facilitates precise diagnosis, monitors safety, demonstrates target engagement, and supports disease modification. OBJECTIVE: This study analyzed the utilization state and trends of biomarkers as endpoints in AD trials...

This study presents a new multifunctional nanofibrous drug delivery system to provide effective combination therapy with enormous potential for the treatment of osteosarcoma. We developed a composite nanofiber scaffold comprising poly(ε-caprolactone) (PCL) and hydroxyapatite (HAp)-loaded doxorubicin (DOX) coated with polydopamine (PDA) to combine cancer cell inhibition with bone tissue regeneration. DOX was conjugated with HAp and then mixed with a PCL solution to prepare a PCL/HAp-DOX (labeled PCLDH) nanofiber...

Empty large volume parenteral (LVP) bottle has irregular shape and narrow opening, and its detection accuracy of the foreign substances at the bottom is higher than that of ordinary packaging bottles. The current traditional detection method for the bottom of LVP bottles is to directly use manual visual inspection, which involves high labor intensity and is prone to visual fatigue and quality fluctuations, resulting in limited applicability for the detection of the bottom of LVP bottles. A geometric constraint-based detection model (GCBDM) has been proposed, which combines the imaging model and the shape characteristics of the bottle to construct a constraint model of the imaging parameters, according to the detection accuracy and the field of view...

The regioselective modification of polyols allows rapid access to their derivatives, thereby accelerating the polyol-related biology and drug discovery. We previously reported that benzoxaborole is a potent catalyst for the regioselective modification of polyols containing a cis -1,2-diol structure. In this study, we developed a bifunctional benzoxaborole catalyst embedded with a Lewis base. Benzoxaborole and Lewis base groups were designed to cooperatively activate a substrate ( cis -1,2-diol) and reactant (electrophile), respectively, hence lowering the reaction barrier for the cis -1,2-diol moiety...

As financial risk protection is one of the goals towards universal health coverage, detailed information on costs, catastrophic costs and other economic consequences related to any disease are required for designing social protection measures. End Tuberculosis (TB) Strategy set a milestone of achieving zero catastrophic cost by 2020. However, a recent literature review noted that 7%-32% TB affected households in India faced catastrophic cost. Studies included in the review were small scale cross-sectional. We followed a cohort of 1482 notified drug-susceptible TB patients from four states in India: Assam, Maharashtra, Tamil Nadu, and West Bengal to provide a comprehensive picture of economic burden associated with TB treatment...

Liver fibrosis is a common pathological feature of most chronic liver diseases with no effective drugs available. Phosphodiesterase 1 (PDE1), a subfamily of the PDE super enzyme, might work as a potent target for liver fibrosis by regulating the concentration of cAMP and cGMP. However, there are few PDE1 selective inhibitors, and none has been investigated for liver fibrosis treatment yet. Herein, compound AG-205/1186117 with the dihydropyrimidine scaffold was selected as the hit by virtual screening. A hit-to-lead structural modification led to a series of dihydropyrimidine derivatives...

Microneedles for skin regeneration are conventionally restricted by uncontrollable multi-drug release, limited types of drugs, and poor wound adhesion. Here, a novel core-shell microneedle patch is developed for scarless skin repair, where the shell is composed of hydrophilic gelatin methacryloyl (GelMA) loaded with mangiferin, an anti-inflammatory small molecule, and the core is composed of hydrophobic poly (lactide- co -propylene glycol- co -lactide) dimethacrylates (PGLADMA) loaded with bioactive macromolecule and human mesenchymal stromal cell (hMSC)-derived exosomes...

Diabetes mellitus (DM) and premenstrual syndrome (PMS) are global health challenges. Both disorders are often linked to a range of physical and psychological symptoms that significantly impact the quality of life of many women. Yet, the exact relation between DM and PMS is not clear, and the management of both conditions poses a considerable challenge. In this review, we aimed to investigate the interplay between DM, anti-diabetic drugs, and the different theories and symptoms of PMS. Female sex hormones are implicated in the pathophysiology of PMS and can also impair blood glucose control...

G-quadruplexes are noncanonical four-stranded DNA secondary structures. MYC is a master oncogene and the G-quadruplex formed in the MYC promoter functions as a transcriptional silencer and can be stabilized by small molecules. We have previously revealed a novel mechanism of action for indenoisoquinoline anticancer drugs, dual-downregulation of MYC and inhibition of topoisomerase I. Herein, we report the design and synthesis of novel 7-aza-8,9-methylenedioxyindenoisoquinolines based on desirable substituents and π-π stacking interactions...

The 3CL protease (3CLpro) is a viral cysteine protease of SARS-CoV-2 and is responsible for the main processing of the viral polyproteins involved in viral replication and proliferation. Despite the importance of 3CLpro as a drug target, the intracellular dynamics of active 3CLpro, including its expression and subcellular localization in SARS-CoV-2-infected cells, are poorly understood. Herein, we report an activity-based probe (ABP) with a clickable alkyne and an irreversible warhead for the SARS-CoV-2 3CL protease...

Biomonitoring of human populations exposed to chemical substances that can act as potential mutagens or carcinogens, may enable the detection of damage and early disease prevention. In recent years, the comet assay has become an important tool for assessing DNA damage, both in environmental and occupational exposure contexts. To evidence the role of the comet assay in human biomonitoring, we have analysed original research studies of environmental or occupational exposure that used the comet assay in their assessments, following the PRISMA-ScR method (preferred reporting items for systematic reviews and meta-analyses extension for scoping reviews)...

Dry eye disease (DED) incidence is continuously growing, positioning it to become an emergent health issue over the next few years. Several topical treatments are commonly used to treat DED; however, reports indicate that only a minor proportion of drug bioavailability is achieved by the majority of eye drops available on the market. In this context, enhancing drug ability to overcome ocular barriers and prolonging its residence time on the ocular surface represent a new challenge in the field of ocular carrier systems...

In the past decade, a lot of insight was gathered into the composition of the host and tumor factors that promote oncogenesis and treatment resistance. This in turn has led to the ingenious design of multiple new classes of drugs, which have now become the new standards of care in cancer therapy. These include novel antibody-drug conjugates, chimeric antigen receptor T cell therapies (CAR-T), and bispecific T cell engagers (BitTE). Certain host factors, such as the microbiome composition, are also emerging not only as biomarkers for the response and toxicity to anti-cancer therapies but also as potentially useful tools to modulate anti-tumor responses...

Multi-criteria decision analysis (MCDA) is a value assessment tool designed to help support complex decision-making by incorporating multiple factors and perspectives in a transparent, structured approach. We developed an MCDA rating tool, consisting of seven criteria evaluating the importance and feasibility of conducting potential real-world evidence (RWE) studies aimed at addressing uncertainties stemming from initial cancer drug funding recommendations. In collaboration with the Canadian Agency for Drugs and Technologies in Health's Provincial Advisory Group, a validation exercise was conducted to further evaluate the application of the rating tool using RWE proposals varying in complexity...

Techniques for extracting important bioactive molecules from seafood byproducts, viz., bones, heads, skin, frames, fins, shells, guts, and viscera, are receiving emphasis due to the need for better valorization. Employing green extraction technologies for efficient and quality production of these bioactive molecules is also strictly required. Hence, understanding the extraction process parameters to effectively design an applicable optimization strategy could enable these improvements. In this review, statistical optimization strategies applied for the extraction process parameters of obtaining bioactive molecules from seafood byproducts are focused upon...

In this study, Antarctic Latrunculia sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis...