Alzheimer’s disease (AD) is a neurodegenerative disorder mostly influencing the elderly, and causes death due to dementia. The main pathogenic feature connected with the progression of this multifactorial disease is the weakening of the cholinergic system in the brain. Cholinesterase (ChE) inhibitors are recognized as one of the choices in the treatment of AD. The inhibition of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) were approved as a therapeutic strategy to reduce the symptoms of AD and prevent its progression. The capacity of BChE is not completely known yet; rather, it is accepted to assume a part in a few disorders such as AD. Thus, BChE inhibitors may have a greater role for the treatment of AD in the future. In the present study, 2-(9-acridinylamino)-2-oxoethyl piperazine/piperidine/morpholinecarbodithioate derivatives were synthesized in order to investigate anticholinesterase activity. Eight derivatives demonstrated a specific and promising action against BChE. Furthermore, compound 4n showed inhibitory activity against both enzymes. It was found that the active compounds were well tolerated in the cytotoxicity test. Possible interactions between the lead compound, 4n, and the BChE enzyme were determined through a docking study. The findings obtained within this paper will contribute to the development of new and effective synthetic anti-Alzheimer compounds, and will ideally encourage future screening against AD.
In the field of therapeutic science, thiazoles are of extraordinary importance, because of their potent and significant biological activities. Likewise thiazole and their derivatives are found in various powerful naturally and biologically active compounds which possess a broad spectrum of biological activity therefore, synthesis of this compound is of remarkable concern. This review primarily focuses on the updated research papers reported in literature for the synthesis of thiazole and thiazolyl compounds.Citation: Hussein W, Zitouni TG. Synthesis of new thiazole and thiazolyl derivatives of medicinal significant-a short review. MOJ Biorg Org Chem. 2018;2(2):52-55.
A new series of N-pyridyl-hydrazone derivatives was synthesized by using a simple and efficient method. The final compounds obtained were screened for their inhibitory potency against monoamine oxidase (MAO) A and B. The newly synthesized compounds 2a–2n specifically inhibited monoamine oxidases, displaying notably low IC50 values. Compounds 2i and 2j, with a CF3 and OH group on the 4-position of the phenyl ring, respectively, showed considerable MAO-A and MAO-B inhibitory activities. Compounds 2k, 2l and 2n, with N-methylpyrrole, furan and pyridine moieties instead of the phenyl ring, were the most powerful and specific inhibitors of MAO-A, with IC50 values of 6.12 μM, 10.64 μM and 9.52 μM, respectively. Moreover, these active compounds were found to be non-cytotoxic to NIH/3T3 cells. This study supports future studies aimed at designing MAO inhibitors to obtain more viable medications for neurodegenerative disorders, such as Parkinson’s disease.
Asetilkolinesteraz inhibitörü olarak tiyazolilhidrazon türevleri üzerine çalışma Amaç: Bu çalışmada, tiyazolün bazı hidrazon türevlerinin sentezlerinin ve antikolinesteraz aktivitelerinin araştırılması amaçlandı. Yöntem: Pirol-2-karboksaldehidler tiyosemikarbazit ile etanol içinde direkt olarak reaksiyona tabi tutuldu ve oluşan tiyosemikarbazon, α-bromoasetofenon türevleri ile (Hantzsch reaction) kondanse edilerek, 1-sübstitüe pirol-2-karboksaldehid (4-(4-sübstitüe fenil)-1,3-tiyazol-2-il)hidrazon türevlerini verdi. Bileşiklerin kimyasal yapıları, IR, 1H-NMR ve FAB+-MS spektral verileri ve elementel analiz verileri ile aydınlatıldı. Modifiye edilmiş Ellman spektrofotometrik metodu kullanılarak, elde edilen tüm bileşiklerin asetilkolinesteraz (AChE) inhibisyonları incelendi. Bulgular: Bileşik 1, AChE üzerinde %64.10 (1 mM) and 33.00 (0.1 mM) inhibisyon oranları ve IC50=0.59 mM değeri ile en aktif antikolinesteraz molekül olarak belirlenmiştir. Sonuçlar: Fenil halkası üzerinde para konumundan ve pirol halkasının 1. konumundan sübstitüsyonlar antikolinesteraz etkiyi negatif yönde etkilemiştir. Anahtar sözcükler: Tiyazol, hidrazon, pirol, antikolinesteraz aktivite ABS TRACT Study on thiazolyl-hydrazone derivatives as acetylcholinesterase inhibitors Objective: In this study we aimed to synthesize some hydrazone derivatives of thiazole and to evaluate their anticholinesterase activities. Method: Pyrrole-2-carboxaldehydes were reacted directly with thiosemicarbazide in ethanol and then obtained thiosemicarbazones were condensed with α-bromoacetophenone derivatives (Hantzsch reaction) to give 1-substituted pyrrole-2-carboxaldehyde (4-(4-substituted phenyl)-1,3-thiazol-2-yl) hydrazones. The structures of the obtained compounds were elucidated by using IR, 1H-NMR and FAB+-MS spectral data and elemental analyses results. In the pharmacological studies, anticholinesterase activities of these compounds have been evaluated by using modified Ellman's spectrophotometric method. Results: The compound (1) can be identified as the most active anticholinesterase molecule due to its inhibitory effect on acetylcholinesterase with inhibition percentages of 64.10 (1 mM) and 33.00 (0.1 mM) % and also IC50 value of 0.59 mM. Conclusion: The substitutions on phenyl ring at para position and at first position of pyrrole ring have negatively affected anticholinesterase activity.
Aim/ Background: Pancreatic lipase (PL) inhibition has been suggested to be an effective method for obesity management. In this study, 10 novel thiazole-benzimidazole conjugates were designed. Materials and Methods: Conjugates were initially screened via in silico experiments, such as ADMET analysis and molecular docking, to identify the most promising PL inhibitors. Results: Results revealed that compounds 3, 6 and 8 had the most optimum druglikeness properties, and the highest binding affinity to PL, with binding energies of -7.7, -7.5 and -8.1 kcal/mol, respectively. Therefore, these promising derivatives were then synthesized and subjected to an in PL inhibition assay to validate the results of the in silico experiments. The synthetic compounds were fully characterized via FTIR, 1 H-NMR, 13 C-NMR and LCMS. Results of the enzymatic assay revealed that 3, 6 and 8 inhibited PL potently with high inhibition rates of greater than 80% at the highest tested dose, and demonstrated IC 50 values of 68.53, 54.97 and 50.09 μM, respectively. Compound 8 was the most active derivative and displayed comparable activity to orlistat which possessed an IC 50 value of 39.18μM. Conclusion: Therefore, we report the discovery of compound 8 as a highly potent PL inhibitor that could act as a lead compound to develop novel anti-obesity agents.
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