The Unveiling of Therapeutic Targets for Alzheimer's Disease: An Integrative Review.

Alzheimer's disease (AD) is characterized by a complex pathological landscape, necessitating a comprehensive treatment approach. This concise review paper delves into the idea of addressing multiple mechanisms in AD, summarizing the latest research findings on pathogenesis, risk factors, diagnostics, and therapeutic strategies. The etiology of AD is multifaceted, involving genetic, environmental, and lifestyle factors. The primary feature is the accumulation of amyloid-- beta and tau proteins, leading to neuroinflammation, synaptic dysfunction, oxidative stress, and neuronal loss. Conventional single-target therapies have shown limited effectiveness, prompting a shift toward simultaneously addressing multiple disease-related processes. Recent advancements in AD research underscore the potential of multifaceted therapies. This review explores strategies targeting both tau aggregation and amyloid-beta, along with interventions to alleviate neuroinflammation, enhance synaptic function, and reduce oxidative stress. In conclusion, the review emphasizes the growing importance of addressing various pathways in AD treatment. A holistic approach that targets different aspects of the disease holds promise for developing effective treatments and improving the quality of life for Alzheimer's patients and their caregivers.

Synthesis and computational insights of flavone derivatives as potential estrogen receptor alpha (ER-α) antagonist.

Hormone-related breast cancer is mostly caused by interactions with estrogen receptor alpha (ER-α), which functions as a transcription factor to control the transcription of numerous genes. Flavones are considered a good substrate for the estrogen receptor. Substitution of the N-heterocyclic ring on the flavon structure may potentiate its anticancer effect. A series of flavon derivatives with an N-heteroaryl ring at the 4' position of the B ring of flavon were designed, prepared and evaluated for in vitro breast cancer activity. Binding interactions of the PzFL, PzF, PiFL, PiF and IFL compounds with ER-α were studied by molecular docking. Molecular dynamics simulation studies were carried out in order to determine the stability and convergence of protein-ligand complexes. The compounds were produced by cyclizing chalcones and chalcones were produced by Claisen-Schmidt condensation of substituted aldehydes and 2-hydroxy acetophenone. Breast cancer activity was evaluated by the MTT assay on MCF-7 cell lines. Also, compounds were studied for their estrogen receptor binding potential on the same cell lines. Molecular docking of compounds showed a good docking score. The molecular dynamics of these compounds expressed stable root mean square deviation, stable radius of gyration and low binding energy, suggesting that ligand bound to protein is quite stable in the complex. MTT assay on MCF-7 cell lines reported PzF and IFL were the most active compounds with lower IC50 values. ER-α binding assay of these compounds revealed the presence of binding interactions with receptors. This study offers a viable reference point for the design of flavon-incorporated N-heterocyclic ring derivatives as breast cancer compounds.Communicated by Ramaswamy H. Sarma.

1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE), doxorubicin and folic acid conjugated micelles for cancer management in tumor bearing BALB/c mice.

Aim of the present investigation was to assess and compare the in-vitro and in-vivo cancer targeting propensity of DPPE-FA-DOX Micelles and free DOX in tumor bearing BALB/c mice. The DOX was conjugated with 1, 2-Dihexadecanoyl-sn-glycero-3-phosphoethanolamin (DPPE) and folic acid using Di-cyclohexyl-carbodiimide, confirmed by Fourier transform infrared spectroscopy (FTIR) and proton NMR. DPPE-FA-DOX micelles were prepared using thin film method and evaluated for zeta potential, particle size, surface morphology, in- vitro drug release study etc. In-vitro anticancer activity and apoptosis assay was evaluated in breast cancer (MCF-7) cells using MTT assay and flow cytometer respectively. In-vivo biodistribution and toxicity assessment were evaluated in rats whereas antitumor activity in tumor bearing BALB/c mice. Prepared micelles were spherical with size and zeta potential of 295.6 + 84.4 nm and 0.8 ± 0.24 mV respectively. Apoptosis assay for DPPE-FA-DOX micelles treated cells using Annexin V/PI staining demonstrated 56.2% apoptotic cells. Remarkably, DPPE-FA-DOX micelles improved DOX bioavailability by 7 fold and diminished plasma elimination with no sign of tissue toxicity compared to free DOX. In-vivo biodistribution studies revealed that micelles facilitated higher accumulation of DOX in tumor than free DOX. DPPE-FA-DOX micelles treated mice survived for 62 days than Free DOX (40 days), revealed by Kaplan-Meier survival curve analysis. Histopathological examination of liver, kidney and heart tissues of micelles treated rat's corroborated reduced systemic toxicity than free DOX. Conclusively, DPPE-FA-DOX micelles could potentially facilitate the targeted delivery of DOX to tumors.

Facile synthesis of mesoporous alumina using hexadecyltrimethylammonium bromide (HTAB) as template: simplified sol-gel approach.

Herein the authors present the synthesis of surface functionalised mesoporous alumina (MeAl) for textural characterisation by a simplified sol-gel method obtained by using hexadecyltrimethylammonium bromide as a template. Etoricoxib (ETOX) was used as a model drug for the study. Alumina supported mesoporous material containing drug was characterised using instrumental technique namely Brunauer-Emmett-Teller surface area, Fourier transform-infrared, differential scanning calorimetry, transmission electron microscopy, X-ray diffraction, and field emission scanning electron microscopy. Diffusion study using a dialysis bag method used to check the release pattern of ETOX-loaded-MeAl. Results of characterisation study revealed the successful surface functionalisation of the drug on nanocomposite. The IC50 value obtained from cell viability study demonstrated the non-toxic behaviour of synthesised drug-loaded mesoporous alumina up to the tested concentration range. The present work has demonstrated that synthesised MeAl showed excellent stability with an expanded surface area suitable for carrier material for drug delivery system.

Facile synthesis of multi-walled carbon nanotube via folic acid grafted nanoparticle for precise delivery of doxorubicin.

The motive of work was to develop a multi-walled carbon nanoplatform through facile method for transportation of potential anticancer drug doxorubicin (DOX). Folic acid (FA)-ethylene diamine (EDA) anchored and acid functionalised MWCNTs were covalently grafted with DOX via π-π stacking interaction. The resultant composite was corroborated by 1H NMR, FTIR, XRD, EDX, SEM, and DSC study. The drug entrapment efficiency of FA-conjugated MWCNT was found high and stability study revealed its suitability in biological system. FA-EDA-MWCNTs-DOX conjugate demonstrated a significant in vitro anticancer activity on human breast cancer MCF-7 cells. MTT study revealed the lesser cytotoxicity of folate-conjugated MWCNTs. The obtained results demonstrated the targeting specificity of FA-conjugate via overexpressed folate receptor deemed greater scientific value to overcome multidrug protection during cancer therapy. The proposed strategy is a gentle contribution towards development of biocompatible targeted drug delivery and offers potential to address the current challenges in cancer therapy.