Development of optimized pyrimido-thiazole scaffold derivatives as anticancer and multitargeting tyrosine kinase inhibitors using computational studies

Asgaonkar, Kalyani; Tanksali, Sushruti; Abhang, Kshitija; Sagar, Ashwini

doi:10.1016/j.jics.2022.100803

Cited by 4 publications

(2 citation statements)

References 48 publications

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“…This investigation provides preliminary data on possible adverse effects of phytocompounds that may be used in the discovery and development of new drugs. 49 , 50 …”

Section: Methodsmentioning

confidence: 99%

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

Mukhtar,

Khan,

Ibisanmi

et al. 2024

Bioinform Biol Insights

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Viral infections and associated illnesses account for approximately 3.5 million global fatalities and public health problems. Medicinal plants, with their wide therapeutic range and minimal side effects, have gained limelight particularly in response to growing concerns about drug resistance and sluggish development of antiviral drugs. This study computationally assessed 11 chemical compounds from Berberis lycium along with two antiviral drugs to inhibit SARS CoV 2 (coronavirus disease 2019 [COVID-19]) RNA-dependent RNA polymerase (RdRP), influenza virus RdRP, and two crucial dengue virus (DENV) enzymes (NS2B/NS3 protease and NS5 polymerase). Berberine and oxyberberine passed all pharmacokinetics analysis filters including Lipinski rule, blood-brain barrier permeant, and cytochrome suppression and demonstrated drug-likeness, bioavailability, and a non-toxic profile. Docking of phytochemicals from B lycium returned promising results with selected viral proteins, ie, DENV NS2BNS3 (punjabine –10.9 kcal/mol), DENV NS5 (punjabine –10.4 kcal/mol), COVID-19 RdRP (oxyacanthine –9.5 kcal/mol), and influenza RdRP (punjabine –10.4 kcal/mol). The optimal pharmacokinetics of berberine exhibited good binding energies with NS2BNS3 (–8.0 kcal/mol), NS5 (–8.3 kcal/mol), COVID RdRP (–7.7 kcal/mol), and influenza RdRP (–8.3 kcal/mol), while molecular dynamics simulation of a 50-ns time scale by GROMACS software package provided insights into the flexibility and stability of the complexes. A hidden treasure trove for antiviral research, berberine, berbamine, berbamunine, oxyberberine, oxyacanthine, baluchistanamine, and sindamine has showed encouraging findings as possible lead compounds. Pharmacological analyses provide credence for the proposed study; nevertheless, as the antiviral mechanisms of action of these phytochemicals are not well understood, additional research and clinical trials are required to demonstrate both their efficacy and toxicity through in vitro and in vivo studies.

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“…This investigation provides preliminary data on possible adverse effects of phytocompounds that may be used in the discovery and development of new drugs. 49 , 50 …”

Section: Methodsmentioning

confidence: 99%

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

Mukhtar,

Khan,

Ibisanmi

et al. 2024

Bioinform Biol Insights

View full text Add to dashboard Cite

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“…Among all the thiazole derivatives, compounds carrying a para group on the phenyl moiety displayed the highest antimicrobial activities [78]. Researchers synthesized and examined various substitutions over the thiazole ring, with 4-ClC 6 H 4 , 4-OCH 3 C 6 H 4 , and 4-CH 3 C 6 H 4 being the preferred substitutions that had a significant impact on the compound's activity [80,81]. In terms of cytotoxicity, compounds with electron-donating substituents in the para position of the benzene ring demonstrated the following trend: OCH 3 > CH 3 [82].…”

Section: Sar Analysis For Synthesized Thiazole Derivativesmentioning

confidence: 99%

Green Synthesis and Molecular Docking Study of Some New Thiazoles Using Terephthalohydrazide Chitosan Hydrogel as Ecofriendly Biopolymeric Catalyst

Al-Humaidi,

Gomha,

El-Ghany

et al. 2023

Catalysts

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Terephthalohydrazide chitosan hydrogel (TCs) was prepared and investigated as an ecofriendly biopolymeric catalyst for synthesis of some novel thiazole and thiadiazole derivatives. Thus, TCs was used as a promising ecofriendly basic biocatalyst for preparation of three new series of thiazoles and two thiadiazoles derivatives via reacting 2-(2-oxo-1,2-diphenylethylidene) hydrazine-1-carbothio-amide with various hydrazonoyl chlorides and α-haloketones under mild ultrasonic irradiation. Also, their yield% was estimated using chitosan and TCs in a comparative study. The procedure being employed has the advantages of mild reaction conditions, quick reaction durations, and high reaction yields. It also benefits from the catalyst’s capacity to be reused several times without significantly losing potency. The chemical structures of the newly prepared compounds were confirmed by IR, MS, and 1H-NMR. Docking analyses of the synthesized compounds’ binding modes revealed promising binding scores against the various amino acids of the selected protein (PDB Code—1JIJ). SwissADME’s online tool is then used to analyze the physiochemical and pharmacokinetic characteristics of the most significant substances. The majority of novel compounds showed zero violation from Lipinski’s rule (Ro5).

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Anticancer and Antibacterial Activeness of Fused Pyrimidines: Newfangled Updates

Bhatnagar,

Pemawat

2024

Bioorganic Chemistry

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Development of optimized pyrimido-thiazole scaffold derivatives as anticancer and multitargeting tyrosine kinase inhibitors using computational studies

Cited by 4 publications

References 48 publications

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

Computational Exploration of Berberis lycium Royle: A Hidden Treasure Trove for Antiviral Development

Green Synthesis and Molecular Docking Study of Some New Thiazoles Using Terephthalohydrazide Chitosan Hydrogel as Ecofriendly Biopolymeric Catalyst

Anticancer and Antibacterial Activeness of Fused Pyrimidines: Newfangled Updates

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