Life Sciences & Biotechnology
Title : | synthesis and evaluation of novel dual GsK-3β/HDAC inhibitor as an anti-Alzheimer agent |
Area of research : | Life Sciences & Biotechnology |
Principal Investigator : | Dr. Abha sharma, National Institute Of Pharmaceutical Education And Research (NIPER) Raebareli, Uttar Pradesh |
Timeline Start Year : | 2023 |
Timeline End Year : | 2026 |
Contact info : | abha.sharma@niperraebareli.edu.in |
Details
Executive Summary : | Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder, approved drugs show improvement in cognition and memory of AD patients but do not stop the progression of AD or reversed the AD symptoms, and according to World Alzheimer Report 2021, the expected number of people suffering from AD would be 152 million by the year 2050. The multi-target strategy is considered a more effective and promising approach for designing a new molecule for modulating the interconnected targets of the AD. Therefore, for developing a new chemical entity, based on literature reports and in silico study, a dual classical GsK-3β/epigenetic HDAC6 inhibitor is designed with the objectives of synthesis of pyrimidone-based series of derivatives and their biological study (in vitro and in vivo). The preliminary in silico study suggested that designed molecules have a binding affinity with the target proteins, predicted toxicity profile, and drug-likeness properties were also found promising. The series of molecules will be synthesized by the proposed four multistep schemes. The enzymatic GsK3β/HDAC assays, toxicity study on cell lines, acute toxicity, memory and cognitive improvement evaluation of scopolamine-induced cognitive deficit, and biochemical evaluation will be done. Only one international research study (2019) is reported for dual inhibitors of GsK3β/HDAC and no report from India is available to the best of our literature review. Hence, exploring this research area for finding out novel molecules that could be simultaneously modulated the multiple interconnected targets of the complex disease leads to the discovery of more effective pharmacological profile drugs compared to the use of more than one single target drug. The study will be added new findings in this research area with the aim of discovering lead molecules for the treatment of AD. |
Total Budget (INR): | 37,91,040 |
Organizations involved