Shbeer AM

References (2)

Title : Evaluation of pyrimidine\/pyrrolidine-sertraline based hybrids as multitarget anti-Alzheimer agents: In-vitro, in-vivo, and computational studies - Javed_2023_Biomed.Pharmacother_159_114239
Author(s) : Javed MA , Jan MS , Shbeer AM , Al-Ghorbani M , Rauf A , Wilairatana P , Mannan A , Sadiq A , Farooq U , Rashid U
Ref : Biomed Pharmacother , 159 :114239 , 2023
Abstract : Alzheimer's disease (AD) is a complex, multifactorial and most prevalent progressive neurodegenerative ailment. Its multifactorial and complex nature causes the lack of disease modifying drugs. Hence, multi-target drug design strategies have been adopted to halt the progression of AD. In current research, we applied multitarget strategy to tackle multifactorial nature of AD. Rational design and synthesis of framework of hybrids containing Pyrimidine/pyrrolidine-sertraline scaffolds were carried out. The synthesized compounds were further evaluated for their in-vitro enzyme inhibition potential against cholinesterases, monoamine oxidases and beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1). Compound 19 emerged as an optimal multipotent hybrid with IC(50) values of 0.07smicroM, 0.09smicroM, 0.63smicroM, 0.21smicroM and 0.73smicroM against AChE, BChE, MAO-A, MAO-B and BACE-1 respectively. After in-vivo cytotoxicity and in-vitro PAMPA blood brain barrier permeation assays, a number of widely used behavioral assessment tests were also performed for the evaluation of memory and learning.Determination of biochemical parameters showed low levels of acetylcholinesterase by the treatment with synthesized compounds. Furthermore, levels of neurotransmitters such as serotonin, dopamine and noradrenaline were also analyzed. Increased neurotransmitter levels showed the improved short and long-term memory as well as enhanced learning behavior. Docking studies on the target enzymes showed correlation with the experimental in-vitro enzyme inhibition results.
ESTHER : Javed_2023_Biomed.Pharmacother_159_114239
PubMedSearch : Javed_2023_Biomed.Pharmacother_159_114239
PubMedID: 36638595

Title : Computer-Aided Screening of Phytoconstituents from Ocimum tenuiflorum against Diabetes Mellitus Targeting DPP4 Inhibition: A Combination of Molecular Docking, Molecular Dynamics, and Pharmacokinetics Approaches - Sajal_2022_Molecules_27_
Author(s) : Sajal H , Patil SM , Raj R , Shbeer AM , Ageel M , Ramu R
Ref : Molecules , 27 : , 2022
Abstract : Diabetes mellitus is a major global health concern in the current scenario which is chiefly characterized by the rise in blood sugar levels or hyperglycemia. In the context, DPP4 enzyme plays a critical role in glucose homeostasis. DPP4 targets and inactivates incretin hormones such as glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) as physiological substrates, which are essential to regulate the amount of insulin that is secreted after eating. Since the inactivation of incretins occurs, the hyperglycemic conditions continue to rise, and result in adverse physiological conditions linked with diabetes mellitus. Hence, inhibition of DPP4 has been the center of focus in the present antidiabetic studies. Although few DPP4 inhibitor drugs, such as alogliptin, saxagliptin, linagliptin, and sitagliptin, are available, their adverse effects on human metabolism are undeniable. Therefore, it becomes essential for the phytochemical intervention of the disease using computational methods prior to performing in vitro and in vivo studies. In this regard, we used an in-silico approach involving molecular docking, molecular dynamics simulations, and binding free energy calculations to investigate the inhibitory potential of Ocimum tenuiflorum phytocompounds against DPP4. In this regard, three phytocompounds (1S-alpha-pinene, beta-pinene, and dehydro-p-cymene) from O. tenuiflorum have been discovered as the potential inhibitors of the DPP4 protein. To summarize, from our in-silico experiment outcomes, we propose dehydro-p-cymene as the potential lead inhibitor of DPP4 protein, thereby discovering new a phytocompound for the effective management of hyperglycemia and diabetes mellitus. The reported compound can be taken for in vitro and in vivo analyses in near future.
ESTHER : Sajal_2022_Molecules_27_
PubMedSearch : Sajal_2022_Molecules_27_
PubMedID: 36014373