3D-QSAR and Molecular Docking Studies of p-Aminobenzoic Acid Derivatives to Explore the Features Requirements of Alzheimer Inhibitors

Khatabi, Khalil El; Aanouz, İlham; El-Mernissi, Reda; Khaldan, Ayoub; Ajana, Mohammed Aziz; Bouachrine, Mohammed; Lakhlifi, Tahar

doi:10.17807/orbital.v12i4.1467

Cited by 10 publications

(6 citation statements)

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“…The crystal structure 7C6S was provided by the RSCB Protein Data Bank (https://www.rcsb.org/). Using the Discovery Studio 2016 software, all water molecules and the original ligand were removed from the protein, and the binding modes were visualized using PyMOL software[15,16]. The preparation steps for docking protocol were used to set up molecular docking with default parameters.…”

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confidence: 99%

Assessment of asthma treatment against SARS CoV-2 by using a computer approach

Hajji

Khatabi

Zaki³

et al. 2021

E3S Web Conf.

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The disease caused by the coronavirus is called COVID-19. The degree of infection varies from one person to another. According to the data collected to date, people with asthma and obesity are over-represented among adults hospitalized for COVID-19. The reason is very simple: COVID-19 is a disease that particularly attacks the respiratory system, including the lungs. This pandemic has led us to return to plants. Modern medicine has found its success thanks to traditional medicine, the effectiveness of which comes from medicinal plants. Currently, in China, many people believe in the miraculous power of plants, boosting their immunity to protect against asthma. Therefore, this work aimed to study components of natural origin that have an anti-asthma effect that can be considered as the panacea against Covid-19, by using the most important method, which is molecular docking. In this research, we performed a molecular docking study on molecules naturally occurring molecules based on the recently crystallized SARS CoV-2 protein (pdb code 7C6S). ADMET prediction was performed for the selected inhibitors. The results of molecular docking and ADMET prediction support the potential of the five selected molecules to be further developed as novel inhibitors for the treatment of SARS CoV-2.

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confidence: 99%

Assessment of asthma treatment against SARS CoV-2 by using a computer approach

Hajji

Khatabi

Zaki³

et al. 2021

E3S Web Conf.

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“…For cognitive function, acetylcholine (ACh) is an important neurotransmitter, so enhancing acetylcholine levels at synapses is the primary treatment [22]. Recently, PABA has been featured as an important inhibitor of cholinesterase [23]. Several p-aminobenzoic acid derivatives have been evaluated against acetylcholinesterase (AChE) for AD treatment.…”

Section: P-aminobenzoic Acid As a Biological Scaffoldmentioning

confidence: 99%

“…The synthesized compound on further reaction gave hydrazine carboxamide benzoic acid derivatives [25]. Hydrazine carboxamide ben-zoic acid derivatives were prepared as presented in Scheme 1 [23]. Derivatives of Schiff bases were synthesized as aminobenzoic acid while ethyl ester was prepared by reacting with carboxylate derivatives under the microwave irradiation synthesis method to yield benzoate, which, upon further reaction with the bromoacetic acid, resulted in triazolyl benzoate derivatives.…”

Section: Synthesis Of Anti-cholinesterase Agentsmentioning

confidence: 99%

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Novel Para-Aminobenzoic Acid Analogs and Their Potential Therapeutic Applications

Haroon,

Farwa,

Arif

et al. 2023

Biomedicines

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A “building block” is a key component that plays a substantial and critical function in the pharmaceutical research and development industry. Given its structural versatility and ability to undergo substitutions at both the amino and carboxyl groups, para-aminobenzoic acid (PABA) is a commonly used building block in pharmaceuticals. Therefore, it is great for the development of a wide range of novel molecules with potential medical applications. Anticancer, anti-Alzheimer’s, antibacterial, antiviral, antioxidant, and anti-inflammatory properties have been observed in PABA compounds, suggesting their potential as therapeutic agents in future clinical trials. PABA-based therapeutic chemicals as molecular targets and their usage in biological processes are the primary focus of this review study. PABA’s unique features make it a strong candidate for inclusion in a massive chemical database of molecules having drug-like effects. Based on the current literature, further investigation is needed to evaluate the safety and efficacy of PABA derivatives in clinical investigations and better understand the specific mechanism of action revealed by these compounds.

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“…One of the most critical steps in deriving stable and reliable 3D-QSAR models is 3D structural alignment. The simple alignment method was used to align the compounds [22], in which the most active compound 6 was served as a structural template for the alignment of the remaining compounds in the data set. The minimized structures were employed as the primal conformations for 3D-QSAR analyses.…”

Section: Molecular Alignmentmentioning

confidence: 99%

2-Oxoquinoline Arylaminothiazole Derivatives in Identifying Novel Potential Anticancer Agents by Applying 3D-QSAR, Docking, and Molecular Dynamics Simulation Studies

et al. 2021

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Abstract. Tubulin plays an indispensable role in regulating various important cellular processes. Recently, it is known as a hopeful therapeutic target for the rapid division of cancer cells. Novel series of 2-oxoquinoline arylaminothiazole derivatives have been recently identified as promising tubulin inhibitors with potent cytotoxicity activity against HeLa cancer cell line. In this study, a 3D-QSAR approach by using CoMFA and CoMSIA techniques was applied to the reported derivatives to understand their pharmacological essentiality contributing to the tubulin inhibition activity and selectivity. The optimum CoMFA and CoMSIA models were found to have signiﬁcant statistical reliability and high predictive ability after internal and external validation. By analyzing the contour maps, the electrostatic and hydrophobic interactions were found to be crucial for improving the inhibitory activity and four novel tubulin inhibitors (Compounds D1, D2, D3, and D4) were designed based on the validated 3D-QSAR models. Moreover, the docking findings showed that residues Gln136, Val238, Thr239, Asn167, Val 318 and Ala 316 played important roles for quinoline binding to tubulin. Among the newly designed compounds, compound D1 with the highest total scoring was subjected to detailed molecular dynamics (MD) simulation and compared to the most active compound. The conformational stability of compound D1 complexed with tubulin protein was confirmed by a 50-ns molecular dynamics simulation, which was congruent with molecular docking. Resumen. La tubulina juega un papel indispensable en la regulación de varios procesos celulares importantes. Recientemente, se le ha reconicodo como un agente promisorio para atacar la rápida división de las células cancerosas. Últimamente se ha identificado una nueva serie de derivados de arilaminotiazo-2-oxoquinolina como potenciales inhibidores de la tubulina, con una elevada actividad citotóxica contra la línea celular de cáncer HeLa. En este estudio, se aplicó a los derivados informados un estudio 3D-QSAR mediante el uso de técnicas CoMFA y CoMSIA para comprender los factores farmacológicos que contribuyen a la actividad como inhibidor y selectivo de la tubulina. Se encontró que los modelos CoMFA y CoMSIA óptimos tienen una confiabilidad estadística significativa y una alta capacidad predictiva después de la validación interna y externa. Al analizar los mapas de contorno, se descubrió que las interacciones electrostáticas e hidrófobas eran cruciales para mejorar la actividad inhibidora y se diseñaron cuatro nuevos inhibidores de la tubulina (compuestos D1, D2, D3 y D4) basados en los modelos 3D-QSAR validados. Además, los hallazgos de acoplamiento mostraron que los residuos Gln136, Val238, Thr239, Asn167, Val 318 y Ala 316 desempeñaron papeles importantes en la unión de la quinolina a la tubulina. Entre los compuestos de nuevo diseño, el compuesto D1 con la puntuación total más alta se sometió a una simulación detallada de dinámica molecular (MD) y se comparó con el compuesto más activo. La estabilidad conformacional del compuesto D1 unido a la proteína tubulina se confirmó mediante una simulación de dinámica molecular de 50 ns, que fue congruente con el acoplamiento molecular.

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3D-QSAR and Molecular Docking Studies of p-Aminobenzoic Acid Derivatives to Explore the Features Requirements of Alzheimer Inhibitors

Cited by 10 publications

References 0 publications

Assessment of asthma treatment against SARS CoV-2 by using a computer approach

Assessment of asthma treatment against SARS CoV-2 by using a computer approach

Novel Para-Aminobenzoic Acid Analogs and Their Potential Therapeutic Applications

2-Oxoquinoline Arylaminothiazole Derivatives in Identifying Novel Potential Anticancer Agents by Applying 3D-QSAR, Docking, and Molecular Dynamics Simulation Studies

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