Viswas Raja Solomon

Introduction: The design of novel therapeutic entities for neurodegenerative diseases, particularly Parkinson’s disease, remains a major challenge in medicinal chemistry. Current treatment strategies primarily rely on symptomatic management, often involving levodopa in combination with catechol-O-methyltransferase (COMT) inhibitors to prolong its therapeutic effect. However, these approaches do not adequately address the multifactorial nature of the disease. This study aims to explore the potential of chalcone derivatives as dual-target-directed ligands capable of modulating both COMT and adenosine A₂A receptors for improved therapeutic outcomes in Parkinson’s disease. Methods: A comprehensive analysis of chalcone-based scaffolds, particularly those incorporating heterocyclic moieties, was undertaken to evaluate their suitability as multitarget agents. Emphasis was placed on their structural versatility and ability to interact with key biological targets involved in Parkinson’s disease pathology. Results: Chalcones exhibit promising pharmacological properties, including the ability to inhibit COMT, thereby reducing levodopa metabolism, and antagonize adenosine A₂A receptors, which play a crucial role in regulating neurotransmission and motor function. Discussion: The incorporation of heterocyclic substituents appears to enhance target affinity and selectivity, likely through improved molecular interactions within the binding site. Furthermore, the observed multitarget activity may confer synergistic therapeutic benefits by concurrently modulating multiple pathological pathways, which is particularly advantageous for the treatment of complex multifactorial diseases. Conclusion: Chalcone derivatives represent a promising class of multitarget compounds for Parkinson’s disease management. Their dual inhibitory activity against COMT and A₂A receptors, combined with their structural flexibility, supports their potential for further development as effective neuroprotective agents.

Background: Increasing antifungal resistance, poor mucosal retention, and systemic side effects limit the effectiveness of currently available drugs. This study explores a novel topical nanotherapeutic approach for the targeted treatment of vulvovaginal candidiasis (VVC), employing green-synthesized silver nanoparticles (AgNPs) derived from Ascophyllum nodosum (AN) and incorporating ibrexafungerp citrate (IBC) into a liposomal formulation. Methods: AgNPs were biosynthesized using AN extract and characterized. Liposomes were prepared by thin-film hydration, and optimised using Central Composite design and characterized and optimized. Optimised liposomes, co-loaded with IBC and AN-AgNPs, were incorporated into a Carbopol-CMC-based topical gel. Results: FTIR shifts in the –OH (3332.31 cm⁻¹) and carbonyl (1636.87 cm⁻¹) bands with reduced intensity confirmed their involvement in Ag⁺ reduction and nanoparticle surface coordination, while the persistence of the 1015 cm⁻¹ band indicated the role of polysaccharides in capping and stabilizing the AN-AgNP. Characterization of the optimized liposomes (IBCL-11) revealed a particle size of 127.2 nm, a zeta potential of −43.8 mV, and a polydispersity index (PDI) of 0.35. Transmission Electron Microscopy (TEM) confirmed the presence of intact, spherical vesicles, while Differential Scanning Calorimetry (DSC) and X-ray diffraction (XRD) validated the molecular dispersion and amorphous characteristics of the films. In vitro evaluations of the IBC liposomal gel demonstrated a sustained drug release of 72.6% over 24 h, alongside enhanced drug penetration across all skin layers. Antifungal assays highlighted the formulation’s potent efficacy, yielding Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) values below 1 µg/mL. Furthermore, the treatments exhibited strong anti-biofilm properties; at MIC and MBC levels, AN-AgNPs achieved biofilm reductions of 45.27 ± 3.16% and 27.62 ± 2.13%, respectively, whereas IBCL-11 produced reductions of 34.25 ± 2.43% and 16.28 ± 1.72%. Conclusion: Ultimately, this study successfully developed an eco-friendly liposomal formulation co-loaded with AN-AgNPs and IBC, offering a promising and targeted therapeutic approach for the treatment of vulvovaginal candidiasis.

Alzheimer’s disease (AD) is a complex and progressive brain disorder marked by memory loss, cognitive decline, and behavioral changes. One of its defining features is the build-up of amyloid plaques, clumps of β-amyloid (Aβ) peptides, in the brain, along with the formation of neurofibrillary tangles. These Aβ peptides are generated when the amyloid precursor protein (APP) is cleaved by enzymes, with β-secretase (BACE1) playing a key role in the first step of this process. Because BACE1 starts the cascade that leads to harmful Aβ build-up, it has become an important target in the search for effective Alzheimer’s treatments. As Aβ accumulates in neurons, it disrupts communication between brain cells and triggers oxidative stress, which worsens damage and accelerates disease progression. This is often exacerbated by imbalances in metal ions, such as copper and iron. While tacrine, an early acetylcholinesterase inhibitor, has shown benefits in managing AD symptoms, its limitations have led researchers to explore improved versions. One promising direction is the development of tacrine-based hybrid molecules. By combining tacrine with other chemical groups that have anti-β-amyloid (Aβ) effects, antioxidant properties, and metal-chelating properties, scientists aim to create compounds that target multiple aspects of the disease simultaneously. This review examines the emerging potential of tacrine hybrids, particularly their capacity to inhibit BACE1 and prevent Aβ aggregation, providing new hope for more effective and disease-modifying therapies for Alzheimer’s disease.

Breast Cancer Gene 1 (BRCA1) offers a potential approach for ERα repression by blocking cyclin D1’s interaction with ERα, which prevents cells from growing and dividing too rapidly or uncontrollably. When BRCA1 levels are low, BRCA1 mimetics fit into the BRCA1-binding pocket within ERα, mimicking the ability of BRCA1 to inhibit ERα activity. This study aims to identify a novel class of lead molecules for BRCA1 mimetics for ER-positive breast cancer, distinct from conventional antiestrogen therapies in their mechanism of action. In this article, coumarin thiosemicarbazone hybrids were synthesized from 7-hydroxy 4-methyl coumarin/4-hydroxy coumarin and thiosemicarbazide with different aldehydes and evaluated for their ERα repression activity. The most active compounds in the series, 9b, 9l, and 9m, exhibited significant potency with an IC₅₀ value of 14.49 µM, 35.08 µM and 42.12 µM, respectively, compared to raloxifene (reported) as the positive control with an IC₅₀ value of 13.7 µM. The gene expression study confirmed the downregulation of the cyclin D1 gene for the compounds 9l (−0.217) and 9m (−0.214). Similarly, the downregulation of the BCL2 gene for the compounds 9b (−0.373), 9l (−0.320), and 9m (−0.376). Also, molecular docking studies and MMGBSA were performed to determine key interactions between compounds and ERα at the BRCA1 binding pocket (AA 338–387). In silico, ADMET properties were executed to illustrate the druggability and safety of the novel derivatives. In silico, in vitro, and gene expression studies revealed that among all the compounds, 9b, 9l, and 9m are promising candidates for the development of lead molecules targeting ERα inhibitors for breast cancer treatment. Moreover, the concept of ERα repression with small molecules as BRCA1 mimetics is novel. In general, it can be concluded that these compounds can serve as promising leads to the design of potential BRCA1 mimetics.

Versatile gelatin nanofibers: revolutionizing biomedical innovations.