Synthesis of biologically relevant heterocyclic skeletons under solvent-free condition

Tripathi, G.; Kumar, Abhijeet; Rajkhowa, Sanchayita; Tiwari, Vinod

doi:10.1016/b978-0-12-820586-0.00013-3

Cited by 7 publications

(5 citation statements)

References 139 publications

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“…Heterocyclic compounds play an essential role in drug discovery and development, with considerable research dedicated to their synthesis and optimization (Tripathi et al, 2021;Babalola et al, 2021;Adetobi et al, 2022). These compounds, characterized by a ring structure containing atoms of at least two different elements, exhibit diverse pharmacological activities and are integral components of many clinically approved drugs.…”

Section: Introductionmentioning

confidence: 99%

Computational Drug Discovery for Novel Small Molecule Inhibitors Targeting LRRK2 in Parkinson's Disease Treatment

emmanuel,

oluwamayowa,

victoria

et al. 2024

Preprint

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Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the brain, leading to motor and non-motor symptoms. The development of novel pharmacotherapies targeting specific molecular pathways implicated in PD pathogenesis is crucial for disease management. Leucine-rich repeat kinase 2 (LRRK2) has emerged as a promising therapeutic target due to its involvement in both familial and sporadic forms of PD. In this study, we employed computational drug discovery techniques to identify potential small molecule inhibitors targeting LRRK2 for PD treatment. The binding affinities of virtual test compounds with the LRRK2 drug target were assessed, revealing a range of affinities from − 6.8 to -10.2 kcal/mol. Lead compounds, including Compound 7, 14, and 15, exhibited the highest binding affinities (-10.2, -10.1, and − 10.1 kcal/mol, respectively), surpassing those of standard ligands. Molecular docking analysis elucidated the inhibitory properties of selected lead compounds, with C7, C14, and C15 identified as the most potent LRRK2 inhibitors. These compounds demonstrated favorable interactions with specific amino acid residues within the LRRK2 receptor, indicating their potential therapeutic efficacy. The validation of the docking protocol confirmed the accuracy of the computational methodology employed, ensuring reliable predictions of ligand-receptor interactions. Furthermore, the ADMET profile analysis provided insights into the drug-like characteristics and pharmacokinetic properties of selected lead compounds. Despite variations in lipophilicity, water solubility, and bioavailability scores, most test compounds exhibited moderate to high GI absorption potential and skin permeation values, suggesting their suitability for oral administration and blood-brain barrier penetration. Toxicity profile predictions highlighted potential hepatotoxicity and mutagenicity risks associated with selected lead compounds, emphasizing the importance of further experimental validation and optimization. Overall, this study contributes to the identification and characterization of novel small molecule inhibitors targeting LRRK2 for PD treatment, offering valuable insights into the rational design of potential disease-modifying therapies.

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Section: Introductionmentioning

confidence: 99%

Computational Drug Discovery for Novel Small Molecule Inhibitors Targeting LRRK2 in Parkinson's Disease Treatment

emmanuel,

oluwamayowa,

victoria

et al. 2024

Preprint

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“…85 It is made up of a phenyl group, a six-membered ring with one carbon atom, and a benzo[d]thiazole ring, a fivemembered ring with one sulphur atom. 86,87 It is a flexible molecule with a variety of possible uses. 87 It is a flexible molecule with a variety of possible uses e.g.…”

Section: Introductionmentioning

confidence: 99%

“…A group of substances known as benzothiazoles includes the chemical molecule 2‐phenylbenzo[ d ]thiazole 85 . It is made up of a phenyl group, a six‐membered ring with one carbon atom, and a benzo[ d ]thiazole ring, a five‐membered ring with one sulphur atom 86,87 . It is a flexible molecule with a variety of possible uses 87 .…”

Section: Introductionmentioning

confidence: 99%

PolyVinyl alcohol and copper nickel co‐doped titania nanocomposite: Designing, characterization, optical properties, and catalytic application in the synthesis of aryl derivatives of benzothiazole and benzimidazole

Mahajan,

Gupta

2023

Applied Organom Chemis

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The paper examines the properties and potential applications of a nanocomposite material composed of polyvinyl alcohol (PVA) and copper nickel co‐doped titanium dioxide (Cu‐TiO2‐Ni). The material was synthesized using a simple precipitation process, and its properties were characterized using various analytical techniques, including powder X‐ray diffraction, Fourier transform infrared spectroscopy, thermogravimetry analysis, field emission scanning electron microscopy, and high‐resolution tunnelling electron microscopy; Brunauer–Emmett–Teller (BET) surface area was investigated. The results showed that the addition of Cu‐TiO2‐Ni to PVA improved the material's Ultraviolet–visible spectroscopy (UV) absorption properties. Additionally, the PVA/Cu‐TiO2‐Ni nanocomposite material exhibited potential for use in a range of applications, including catalysis. Its utility in synthesizing aryl derivatives of benzothiazole and benzimidazoles, which are crucial intermediates in the fine chemical, agrochemical, and pharmaceutical industries and material science, was evaluated. It was found to offer several advantages, including a quick reaction time, simple workup, and good to excellent isolated yields. These characteristics make this protocol both practical and economically intriguing.

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“…Heterocyclic compounds play an essential role in drug discovery and development; hence, great work has gone into developing simple and environmentally friendly methods for their high yielding production [21]. For example, compounds derived from azetidine have shown to have a diverse range of pharmacological activities, such as anticancer [22], antibacterial [23,24], antimicrobial [25], antischizophrenic [26], antimalarial [27,28], antiobesity [29,30], anti-viral [31], antioxidant [31], and dopamine antagonist [32] activity, amongst others.…”

Section: Introductionmentioning

confidence: 99%

“…Other heterocyclics, such as cyclic amidine and guanidine also possess biological potency [36,37]. Heterocyclic skeletons of promising pharmacological importance usually contain nitrogen, sulphur, and oxygen as they represent a major proportion of the bioactive heterocyclic compounds and marketed drugs [21]. Azetidine, amidine, and gunanine rings are nitrogen-containing heterocyclic organic compounds with different synthetic strategies and pharmaceutical importance [31,32,37,38].…”

Section: Introductionmentioning

confidence: 99%

Computational Study of the Therapeutic Potential of Novel Heterocyclic Derivatives against SARS-CoV-2

Babalola

Adetobi

Akinsuyi

et al. 2021

COVID

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Severe Acute Respiratory Syndrome Coronavirus- 2 (SARS-CoV-2), including the recently reported severe variant B.1.617.2, has been reported to attack the respiratory tract with symptoms that may ultimately lead to death. While studies have been conducted to evaluate therapeutic interventions against the virus, this study evaluated the inhibitory potential of virtually screened novel derivatives and structurally similar compounds towards SARS-CoV-2 via a computational approach. A molecular docking simulation of the inhibitory potentials of the compounds against the SARS-CoV-2 drug targets—main protease (Mpro), spike protein (Spro), and RNA-dependent RNA polymerase (RdRp)—were evaluated and achieved utilizing AutoDock Vina in PyRx workspace. The absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of these compounds were assessed using SwissADME and ADMETLab servers. All the compounds displayed high binding affinities for the SARS-CoV-2 drug targets. However, the C13 exhibited the highest binding affinity for the drug targets, Spro and RdRp, while C15 exhibited the highest binding affinity for Mpro. The compounds interacted with the LEU A:271, LEU A:287, ASP A:289, and LEU A:272 of Mpro and the HIS A:540, PRO A:415, PHE A:486, and LEU A:370 of the Spro receptor binding motif and some active site amino acids of RdRp. The compounds also possess a favourable ADMET profile and showed no tendency towards hERG inhibition, hepatotoxicity, carcinogenicity, mutagenicity, or drug-liver injury. These novel compounds could offer therapeutic benefits against SARS-CoV-2, and wet laboratory experiments are necessary to further validate the results of this computational study.

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Synthesis of biologically relevant heterocyclic skeletons under solvent-free condition

Cited by 7 publications

References 139 publications

Computational Drug Discovery for Novel Small Molecule Inhibitors Targeting LRRK2 in Parkinson's Disease Treatment

Computational Drug Discovery for Novel Small Molecule Inhibitors Targeting LRRK2 in Parkinson's Disease Treatment

PolyVinyl alcohol and copper nickel co‐doped titania nanocomposite: Designing, characterization, optical properties, and catalytic application in the synthesis of aryl derivatives of benzothiazole and benzimidazole

Computational Study of the Therapeutic Potential of Novel Heterocyclic Derivatives against SARS-CoV-2

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