Alzheimer’s disease (AD) is the most common neurodegenerative disease which has a rather complex pathophysiology. During its course, several neurotransmitter neuronal systems get affected such as acetylcholinergic, glutamatergic, gamma-aminobutyric acid (GABA)ergic systems, etc. Such complex physiology requires a sophisticated approach to pharmaceutical management. Therefore, multi-target drugs seem to be an appealing solution. In the present study, we designed and synthesized a hybrid molecule—N-sinapoylamide of memantine, whose parent molecules memantine (MEM) and sinapic acid have been shown in vivo to impact glutamatergic, acetylcholinergic, and GABA-ergic systems, respectively. In silico comparative testing of these molecules was performed, their patterns of interaction with the target enzymes or molecular complexes were analyzed, and some of the mechanisms of action were proposed. Consequently, in vivo testing was performed on a scopolamine mice model of AD and the results overly confirm part of the in silico findings. Therefore, the hybrid molecule (N-Sinapoyl-memantine) seems to be a potent candidate for further evaluation in the management of AD.

Parkinson’s disease (PD) has emerged as the second most common form of human neurodegenerative disorders. However, due to the severe side effects of the current antiparkinsonian drugs, the design of novel and safe compounds is a hot topic amongst the medicinal chemistry community. Herein, a convenient peptide method, TBTU (O-(benzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium tetrafluoroborate), was used for the synthesis of the amide (E)-N-(2-methylcinnamoyl)-amantadine (CA(2-Me)-Am; 3)) derived from amantadine and 2-methylcinnamic acid. The obtained hybrid was studied for its antiparkinsonian activity in an experimental model of PD induced by MPTP. Mice (C57BL/6,male, 8 weeks old) were divided into four groups as follows: (1) the control, treated with normal saline (i.p.) for 12 consecutive days; (2) MPTP (30 mg/kg/day, i.p.), applied daily for 5 consecutive days; (3) MPTP + CA(2-Me)-Am, applied for 12 consecutive days, 5 days simultaneously with MPTP and 7 days after MPTP; (4) CA(2-Me)-Am +oleanoic acid (OA), applied daily for 12 consecutive days. Neurobehavioral parameters in all experimental groups of mice were evaluated by rotarod test and passive avoidance test. Our experimental data showed that CA(2-Me)-Am in parkinsonian mice significantly restored memory performance, while neuromuscular coordination approached the control level, indicating the ameliorating effects of the new compound. In conclusion, the newly synthesized hybrid might be a promising agent for treating motor disturbances and cognitive impairment in experimental PD.

Alzheimer’s disease (AD) is the most common neurodegenerative disease which has rather complex pathophysiology. During its course several neurotransmitter neuronal systems get affected as acetylcholinergic, glutamatergic, gamma-aminobutyric acid (GABA)ergic system and etc. Such complex physiology requires sophisticated approach of pharmaceutical management. Therefore, multi-target drugs seem to be an appealing solution. In the present study we designed and synthesized a hybrid molecule - N-sinapoylamide of memantine, whose parent molecules memantine (MEM) and sinapic acid has been shown in vivo to impact glutamatergic and acetylcholinergic and GABA-ergic systems respectively. In silico comparative testing of these molecules was performed and their patterns of interaction with the target enzymes or molecular complexes were analyzed and some of the mechanisms of action were proposed. Consequently, in vivo testing was performed on scopolamine mice model of AD and the results overly confirm part of the in silico findings. Therefore the hybrid molecule (N-Sinapoyl-memantine) seems to be a potent candidate for further evaluation in the management of AD.

The brain organoid technology emerged a little over a decade ago. During this short time span, the handling approach has seen tremendous advancements in order to solve current obstacles and enable the development of new applications. Using these methodologies, the fundamental characteristics of the majority of the brain regions may be mimicked in organoids; however, the existing brain organoids cannot be regarded an exact replica of the human brain or its anatomical regions. This chapter will present some of the biological phenomena on which the brain organoid technology relies. Following this, a summary of the gross common structure and timeline of the brain organoid protocols along with their main components and strategies for their improvement is included. A special selection of protocols for each major brain region will be presented with their origin, rationale, and key specifics. Finally, some of the daunting challenges to brain organoid technology will be highlighted.

Influenza A viruses that cause pandemics, as well as other harmful pathogens (e.g., SARS-CoV-2 variants), are known as the ‘silent bioterrorists’ of the 21st century. Due to high mutability, anti-influenza chemotherapeutic treatment is a vital defense strategy to combat both seasonal and pandemic influenza strains, especially when vaccines fail. Consequently, the development of novel therapies to combat this serious threat is of great concern. Hence, in this study, 3-(2-thienyl) acrylic acid (TA) was converted into amides of anti-influenza drugs (aminoadamantanes and oseltamivir) through TBTU-mediated coupling. The crystal structures of the thienyl-based amide hybrids (TA-Am (1), TA-Rim (2), TA-Os-OEt (3), and TA-OsC (4)) were also investigated using single-crystal X-ray diffraction, powder X-ray diffraction (PXRD), and differential scanning calorimetry (DSC). Moreover, the antiviral activities of the hybrids against influenza virus A/Fort Monmouth/1/1947 (H1N1), clinically isolated influenza strain A/Wuhan/359/1995 (H3N2), and oseltamivir-resistant A/Jinnan/15/2009 (H1N1) were evaluated in vitro. Amongst the tested thienyl-based amides, bisamide 8 (Boc-Os-Hda-TA) exhibited the most potent activity against influenza virus A (A/Wuhan/359/1995) with an IC₅₀ value of 18.52 μg/mL and a selectivity index (SI) = 13.0.