Oxadiazoles as Privileged Motifs for Promising Anticancer Leads: Recent Advances and Future Prospects

Khan, Imtiaz; Ibrar, Aliya; Abbas, Naeem

doi:10.1002/ardp.201300231

Cited by 63 publications

(20 citation statements)

References 126 publications

(119 reference statements)

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“…Additionally, 1,3,4-oxadiazole has emerged as an important scaffold owing to its metabolic profile and ability to engage in hydrogen bonding with receptor site. Recent studies have indicated that 1,3,4-oxadiazole derivatives exhibit potent anticancer activity against different cancer cell lines through the inhibition of different growth factors, enzymes and kinases including telomerase, histone deacetylase (HDAC), methionine aminopeptidase (MetAP), thymidylate synthase (TS), glycogen synthase kinase-3 (GSK), epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), and focal adhesion kinase (FAK) [24][25][26]. Triazoles [27], tetrazoles [28], thiadiazoles [29], and pyrimidines [4] have also been reported to show anticancer activity.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

et al. 2015

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New pyrazoline derivatives were synthesized and evaluated for their cytotoxic effects on AsPC-1 human pancreatic adenocarcinoma, U87 and U251 human glioblastoma cell lines. 1-[((5-(4-Methylphenyl)-1,3,4-oxadiazol-2-yl)thio)acetyl]-3-(2-thienyl)-5-(4-chlorophenyl)-2-pyrazoline (11) was found to be the most effective anticancer agent against AsPC-1 and U251 cell lines, with IC50 values of 16.8 µM and 11.9 µM, respectively. Tumor selectivity of compound 11 was clearly seen between Jurkat human leukemic T-cell line and human peripheral blood mononuclear cells (PBMC). Due to its promising anticancer activity, compound 11 was chosen for apoptosis/necrosis evaluation and DNA-cleavage analysis in U251 cells. Compound 11-treated U251 cells exhibited apoptotic phenotype at low concentration (1.5 µM). DNA-cleaving efficiency of this ligand was more significant than cisplatin and was clearly enhanced by Fe(II)-H2O2-ascorbic acid systems. This result pointed out the relationship between the DNA cleavage and the cell death.

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Section: Introductionmentioning

confidence: 99%

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

et al. 2015

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“…Chemically, most current synthetic anticancer drugs are heterocyclic compounds and nitrogen heterocycles [9][10][11][12]. This fact is observed by analyzing the chemical structures of some anticancer drugs approved by the FDA (Food and drug administration) in 2017, which share a pyrimidine scaffold as part of their structures (Figure 1).…”

Section: Introductionmentioning

confidence: 99%

Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays

Salas

Zárate

Kryštof

et al. 2019

IJMS

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We designed, synthesized, and evaluated novel 2,6,9-trisubstituted purine derivatives for their prospective role as antitumor compounds. Using simple and efficient methodologies, 31 compounds were obtained. We tested these compounds in vitro to draw conclusions about their cell toxicity on seven cancer cells lines and one non-neoplastic cell line. Structural requirements for antitumor activity on two different cancer cell lines were analyzed with SAR and 3D-QSAR. The 3D-QSAR models showed that steric properties could better explain the cytotoxicity of compounds than electronic properties (70% and 30% of contribution, respectively). From this analysis, we concluded that an arylpiperazinyl system connected at position 6 of the purine ring is beneficial for cytotoxic activity, while the use of bulky systems at position C-2 of the purine is not favorable. Compound 7h was found to be an effective potential agent when compared with a currently marketed drug, cisplatin, in four out of the seven cancer cell lines tested. Compound 7h showed the highest potency, unprecedented selectivity, and complied with all the Lipinski rules. Finally, it was demonstrated that 7h induced apoptosis and caused cell cycle arrest at the S-phase on HL-60 cells. Our study suggests that substitution in the purine core by arylpiperidine moiety is essential to obtain derivatives with potential anticancer activity.

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“…A wide range of biologically active pharmacophores possess these five-membered heteroaromatic ring systems with remarkable biological properties including sphinosine kinase inhibitor [ 29 ], diacylglycerol acyltransferase 1 (DGAT-1) inhibitor [ 30 ], glycogen synthase kinase (GSK-3) inhibitor [ 31 ], sirtuin (SIRT) inhibitor [ 32 ] and methionine aminopeptidase inhibitor activities [ 33 ]. Some diterpenic 1,2,4- and 1,3,4-oxadiazoles, including steroid-based compounds, have also shown remarkable antiproliferative action on adherent human cancer cell lines [ 25 , 26 , 34 , 35 , 36 , 37 ].…”

Section: Introductionmentioning

confidence: 99%

Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles

Gonda

Bérdi

Zupkó

et al. 2017

IJMS

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Stereoselective synthesis of monoterpene-based 1,2,4- and 1,3,4-oxadiazole derivatives was accomplished starting from α,β-unsaturated carboxylic acids, obtained by the oxidation of (−)-2-carene-3-aldehyde and commercially available (−)-myrtenal. 1,2,4-Oxadiazoles were prepared in two steps via the corresponding O-acylamidoxime intermediates, which then underwent cyclisation induced by tetrabutylammonium fluoride (TBAF) under mild reaction conditions. Stereoselective dihydroxylation in highly stereospecific reactions with the OsO4/NMO (N-methylmorpholine N-oxide) system produced α,β-dihydroxy 1,2,4-oxadiazoles. Pinane-based 1,3,4-oxadiazoles were obtained similarly from acids by coupling with acyl hydrazines followed by POCl3-mediated dehydrative ring closure. In the case of the arane counterpart, the rearrangement of the constrained carane system occurred with the loss of chirality under the same conditions. Stereoselective dihydroxylation with OsO4/NMO produced α,β-dihydroxy 1,3,4-oxadiazoles. The prepared diols were applied as chiral catalysts in the enantioselective addition of diethylzinc to aldehydes. All compounds were screened in vitro for their antiproliferative effects against four malignant human adherent cell lines by means of the MTT assay with the O-acylated amidoxime intermediates exerting remarkable antiproliferative action.

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Oxadiazoles as Privileged Motifs for Promising Anticancer Leads: Recent Advances and Future Prospects

Cited by 63 publications

References 126 publications

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

Synthesis and Evaluation of New Pyrazoline Derivatives as Potential Anticancer Agents

Promising 2,6,9-Trisubstituted Purine Derivatives for Anticancer Compounds: Synthesis, 3D-QSAR, and Preliminary Biological Assays

Stereoselective Synthesis, Synthetic and Pharmacological Application of Monoterpene-Based 1,2,4- and 1,3,4-Oxadiazoles

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