Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease

Karaca, Şevval; Osmaniye, Derya; Sağlık, Begüm Nurpelin; Levent, Serkan; Ilgın, Sinem; Özkay, Yusuf; Karaburun, Ahmet Çağrı; Kaplancıklı, Zafer Asım; Gündoğdu-Karaburun, Nalan

doi:10.1039/d2ra03803j

Cited by 18 publications

(13 citation statements)

References 42 publications

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“…Therefore, molecules with benzothiazole group could be capable of making interactions with Aβ 1-42 , such as ThT [ 42 ]. In addition, new benzothiazole derivatives have recently been reported as inhibitors for Aβ 1-42 aggregation and other enzymes for the treatment of AD [ 43 ]. The results obtained by docking simulations depict key interactions with the amino acids involved in the conformational change of Aβ 1-42 , such as D23 and E22, with the benzothiazole-isothiourea.…”

Section: Discussionmentioning

confidence: 99%

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer’s Disease

Rosales‐Hernández

Morales²,

Correa-Basurto³

et al. 2022

IJMS

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Alzheimer’s disease (AD) is a progressive neurodegenerative disorder. Inhibiting acetylcholinesterase (AChE), amyloid beta (Aβ1-42) aggregation and avoiding the oxidative stress could prevent the progression of AD. Benzothiazole groups have shown neuroprotective activity whereas isothioureas groups act as AChE inhibitors and antioxidants. Therefore, 22 benzothiazole-isothiourea derivatives (3a–v) were evaluated by docking simulations as inhibitors of AChE and Aβ1-42 aggregation. In silico studies showed that 3f, 3r and 3t had a delta G (ΔG) value better than curcumin and galantamine on Aβ1-42 and AChE, respectively. The physicochemical and pharmacokinetics predictions showed that only 3t does not violate Lipinski’s rule of five, though it has moderated cytotoxicity activity. Then, 3f, 3r and 3t were synthetized and chemically characterized for their in vitro evaluation including their antioxidant activity and their cytotoxicity in PC12 cells. 3r was able to inhibit AChE, avoid Aβ1-42 aggregation and exhibit antioxidant activity; nevertheless, it showed cytotoxic against PC12 cells. Compound 3t showed the best anti-Aβ1-42 aggregation and inhibitory AChE activity and, despite that predictor, showed that it could be cytotoxic; in vitro with PC12 cell was negative. Therefore, 3t could be employed as a scaffold to develop new molecules with multitarget activity for AD and, due to physicochemical and pharmacokinetics predictions, it could be administered in vivo using liposomes due to is not able to cross the BBB.

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Section: Discussionmentioning

confidence: 99%

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer’s Disease

Rosales‐Hernández

Morales²,

Correa-Basurto³

et al. 2022

IJMS

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“…In 96-well plates, NIH/3T3 cells were seeded at a density of 1 × 10 4 cells per well. The MTT test was conducted in line with the previously mentioned standards. ,,,, …”

Section: Methodsmentioning

confidence: 99%

“…The Beta Amyloid 1–42 (Aβ42) Ligand Screening Assay kit (BioVision, Milpitas, CA) technique based on the fluorometric approach served as the basis for the experimental process. ,, …”

Section: Methodsmentioning

confidence: 99%

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Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

et al. 2022

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Alzheimer’s disease (AD) is a neurological, progressive illness that typically affects the elderly and is clinically distinguished by memory and cognitive decline. Due to a number of factors, including the absence of a radical treatment, an increase in the patient population over time, the high cost of care and treatment, and a significant decline in patients’ quality of life, the importance of this disease has increased. These factors have all prompted increased interest among researchers in this field. The chemical structure of the donepezil molecule, the most popular and effective treatment response for AD, served as the basis for the design and synthesis of 42 novel indan-1-one derivatives in this study. Using IR, 1H, and 13C NMR as well as mass spectroscopic techniques, the compounds’ structures were identified. Research on the compounds’ antioxidant activities, cholinesterase (ChE) enzyme inhibition, monoamine oxidase (MAO) A and B inhibitory activities, β-amyloid plaque inhibition, and cytotoxicity impact was carried out. Inhibition of β-amyloid plaque aggregation; effective inhibition of AChE, BChE, and MAO-B enzymes; and significant antioxidant activity were all demonstrated by compounds D28–D30 and D37–D39. Because of their various actions, it was hypothesized that the related compounds may be useful in treating AD symptoms as well as providing palliative care.

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“…Their derivatives possess various biological activities, including anti-inflammatory, antitubercular, antifungal, and anti-diabetic properties [ 25 , 26 , 27 , 28 ]. Recently, Karaca et al showed that some benzothiazole derivatives have a promising potential for the treatment Alzheimer’s and Parkinson’s diseases [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties—Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities

et al. 2023

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In the search for new bioactive compounds, a methodology based on combining two molecules with biological properties into a new hybrid molecule was used to design and synthesize of a series of ten indole derivatives bearing imidazole, benzothiazole-2-thione, or benzoxazole-2-thione moieties at the C-3 position. The compounds were spectroscopically characterized and tested for their antioxidant, antibacterial, and fungicidal activities. The crystal structures were determined for five of them. Comparison of the closely related structures containing either benzothiazole-2-thione or benzoxazole-2-thione clearly shows that the replacement of -S- and -O- ring atoms modify molecular conformation in the crystal, changes intermolecular interactions, and has a severe impact on biological activity. The results indicate that indole-imidazole derivatives with alkyl substituent exhibit an excellent cytoprotective effect against AAPH-induced oxidative hemolysis and act as effective ferrous ion chelating agents. The indole-imidazole compound with chlorine atoms inhibited the growth of fungal strains: Coriolus versicolor (Cv), Poria placenta (Pp), Coniophora puteana (Cp), and Gloeophyllum trabeum (Gt). The indole-imidazole derivatives showed the highest antibacterial activity, for which the largest growth-inhibition zones were noted in M. luteus and P. fluorescens cultures. The obtained results may be helpful in the development of selective indole derivatives as effective antioxidants and/or antimicrobial agents.

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Synthesis of novel benzothiazole derivatives and investigation of their enzyme inhibitory effects against Alzheimer's disease

Abstract: The use of dual acetylcholinesterase (AChE)–monoamine oxidase B (MAO-B) inhibitors is a new approach in the treatment of Alzheimer disease (AD).

Cited by 18 publications

References 42 publications

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer’s Disease

In Silico and In Vitro Studies of Benzothiazole-Isothioureas Derivatives as a Multitarget Compound for Alzheimer’s Disease

Design, Synthesis, and In Vitro and In Silico Approaches of Novel Indanone Derivatives as Multifunctional Anti-Alzheimer Agents

Indole Derivatives Bearing Imidazole, Benzothiazole-2-Thione or Benzoxazole-2-Thione Moieties—Synthesis, Structure and Evaluation of Their Cytoprotective, Antioxidant, Antibacterial and Fungicidal Activities

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