One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies

Sekhar, T. Chandra; Thriveni, P.; Venkateswarlu, Annavarapu; Thathapudi, Daveedu; Kotha, Peddanna; Sainath, S.B.

doi:10.1016/j.saa.2020.118056

Cited by 28 publications

(7 citation statements)

References 32 publications

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“…119a with IC 50 = 2.2 ± 0.6 μM against A549 and compound 119b with IC 50 = 5.6 ± 0.4 μM against HeLa exhibited better effects than positive control DOX. The presence of methoxyphenyl groups and naphthyl on thiazolopyrimidine demonstrated enhanced activity [122]. Novel thiazolo [3, 2-a] pyrimidines were screened for in vitro antiproliferative The different activity between the compounds was due to variation of substitutions in the phenyl group of the molecule and the presence of sulfur and nitrogen atom subsequently enhanced the activity.…”

Section: Thiazolo [32-a]pyrimidinesmentioning

confidence: 99%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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Background Cancer is a global health challenge, it impacts the quality of life and its treatment is associated with several side effects. Resistance of the cancer cells to the existing drugs has led to search for novel anticancer agents. Pyrimidine, a privileged scaffold, is part of living organisms and plays vital role in various biological procedures as well as in cancer pathogenesis. Due to resemblance in structure with the nucleotide base pair of DNA and RNA, it is recognized as valuable compound in the treatment of cancer. Main text Many novel pyrimidine derivatives have been designed and developed for their anticancer activity in the last few years. The present review aims to focus on the structure activity relationship (SAR) of pyrimidine derivatives as anticancer agent from the last decade. Conclusion This review intends to assist in the development of more potent and efficacious anticancer drugs with pyrimidine scaffold. Graphical abstract

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Section: Thiazolo [32-a]pyrimidinesmentioning

confidence: 99%

Pyrimidine: a review on anticancer activity with key emphasis on SAR

2021

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“…It is well recognized that the thiazolo[3,2- a ]pyrimidine; a fused heterocyclic system consisting of six-membered pyrimidine and five-membered thiazole rings with bridgehead nitrogen atom is a privileged motif found in numerous natural products and various synthetic compounds. In the recent times, it has emerged as a potential synthetic area in heterocyclic synthesis due to its widespread applications among as acetylcholinesterase inhibitor 1 , calcium antagonist 2 , cytotoxic agent 3 , antitubercular, CDC25 phosphatase inhibitor 4 , antidepressant 5 as well as in polymerization reactions as co-polymer 6 – 8 . Although short of literature, the synthesis of thiazolo[3,2- a ]pyrimidine nucleus has been reported by the sodium acetate catalyzed reaction of tetrahydropyrimidine-5( H )-2-thione with α-halo carbonyl compounds 1 , 5 , 9 in acetic acid reflux, 1,1,1,3,4,4,5,5,5-nonafluoro-2-(trifluoromethyl)pent-2-ene 10 in triethylamine catalyzed acetonitrile reflux and by the reaction of aromatic aldehydes with 2-aminothiazole and malononitrile/diethyl malonate/ethyl 2-cyanoacetate in piperidine catalyzed ethanolic reflux 11 , 12 .…”

Section: Introductionmentioning

confidence: 99%

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Aggarwal

Jain

Sharma

et al. 2021

Sci Rep

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In recent times, fused azaheterocycles emerged as impressive therapeutic agents. Binding studies of such azaheterocycles with biomolecules is an important subject for pharmaceutical and biochemical studies aiming at the design and development of new drugs. Fused heterocyclic scaffolds, such as thiazolopyrmidines have long been used in the pharmaceutical industry for the treatment of various diseases. In this study, we have accomplished a regioselective synthesis of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines by the reaction of tetrahydropyrimidine-2(H)-thione with α-bromo-1,3-diketones, generated in situ from 1,3-diketones and NBS, using visible light as an inexpensive, green and renewable energy source under mild reaction conditions with wide-ranging substrate scope. The regioisomer was characterized unambiguously by 2D-NMR [1H-13C] HMBC and [1H-13C] HMQC spectroscopy. In silico toxicity data analysis showed the low toxicity risks of the synthesized compounds. Computational molecular docking studies were carried out to examine the interaction of thiazolo[3,2-a]pyrimidines with calf-thymus DNA (ct-DNA) and Bovine Serum Albumin (BSA). Moreover, different spectroscopic approaches viz. steady-state fluorescence, competitive displacement assay, UV–visible and circular dichroism (CD) along with viscosity measurements were employed to investigate the binding mechanisms of thiazolo[3,2-a]pyrimidines with DNA and BSA. The results thus obtained revealed that thiazolo[3,2-a]pyrimidines offer groove bindings with DNA and showed moderate bindings with BSA.

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“…The appropriate cyclic ketone (1.25 mmol, 1.0 equiv, Scheme S3), N -bromosuccinimide (1.40 mmol, 1.0–1.1 equiv) and p -toluenesulfonic acid (0.13 mmol, 10 mol%) were added to 5 mL of dichloromethane in a 15 mL round-bottom flask. The reaction mixture was stirred at rt for 16 h. The solvent was removed under reduced pressure by rotary evaporation to obtain a residue.…”

Section: Experimental Methodsmentioning

confidence: 99%

“…32 In a 50 mL round-bottom flask equipped with a stir bar were added ethyl 2-cyanoacetate (0.91 mL, 8.54 mmol, 1.0 equiv, Scheme S2), 3-bromo- General Method for Favorskii Rearrangement 59,60 to Prepare 45l,m. The appropriate cyclic ketone (1.25 mmol, 1.0 equiv, Scheme S3), N-bromosuccinimide (1.40 mmol, 1.0− 1.1 equiv) and p-toluenesulfonic acid (0.13 mmol, 10 mol%) 61 were added to 5 mL of dichloromethane in a 15 mL roundbottom flask. The reaction mixture was stirred at rt for 16 h. The solvent was removed under reduced pressure by rotary evaporation to obtain a residue.…”

Section: Synthesis Of 38 By a Sonogashira Reaction Of 35 2-cyclohexyl...mentioning

confidence: 99%

Structure–Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A₃ Adenosine Receptor Positive Allosteric Modulators

et al. 2022

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We previously reported 1H-imidazo[4,5-c]quinolin-4-amines as A 3 adenosine receptor (A 3 AR) positive allosteric modulators (PAMs). A 3 AR agonists, but not PAMs, are in clinical trials for inflammatory diseases and liver conditions. We synthesized new analogues to distinguish 2-cyclopropyl antagonist 17 (orthosteric interaction demonstrated by binding and predicted computationally) from PAMs (derivatives with large 2-alkyl/cycloalkyl/bicycloalkyl groups). We predicted PAM binding at a hydrophobic site on the A 3 AR cytosolic interface. Although having low Caco-2 permeability and high plasma protein binding, hydrophobic 2-cyclohept-4-enyl-N-3,4-dichlorophenyl, MRS7788 18, and 2-heptan-4-yl-N-4-iodophenyl, MRS8054 39, derivatives were orally bioavailable in rat. 2-Heptan-4-yl-N-3,4-dichlorophenyl 14 and 2-cyclononyl-N-3,4-dichlorophenyl 20 derivatives and 39 greatly enhanced Cl-IB-MECA-stimulated [ 35 S]GTPγS binding E max , with only 12b trending toward decreasing the agonist EC 50 . A feasible route for radio-iodination at the p-position of a 4-phenylamino substituent suggests a potential radioligand for allosteric site binding. Herein, we advanced an allosteric approach to developing A 3 AR-activating drugs that are potentially event-and site-specific in action.

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One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies

Cited by 28 publications

References 32 publications

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Structure–Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A₃ Adenosine Receptor Positive Allosteric Modulators

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One-pot synthesis of thiazolo[3,2-a]pyrimidine derivatives, their cytotoxic evaluation and molecular docking studies

Cited by 28 publications

References 32 publications

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Pyrimidine: a review on anticancer activity with key emphasis on SAR

Visible-light driven regioselective synthesis, characterization and binding studies of 2-aroyl-3-methyl-6,7-dihydro-5H-thiazolo[3,2-a]pyrimidines with DNA and BSA using biophysical and computational techniques

Structure–Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A3 Adenosine Receptor Positive Allosteric Modulators

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Structure–Activity Studies of 1H-Imidazo[4,5-c]quinolin-4-amine Derivatives as A₃ Adenosine Receptor Positive Allosteric Modulators