Anticancer activity of newly synthesized 1,2,4-Oxadiazole linked 4-（Oxazolo[5,4-d]pyrimidine derivatives (original) (raw)
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International Journal of Molecular Sciences
Cancer is a large group of diseases in which the rapid proliferation of abnormal cells generally leads to metastasis to surrounding tissues or more distant ones through the lymphatic and blood vessels, making it the second leading cause of death worldwide. The main challenge in designing a modern anticancer therapy is to develop selective compounds that exploit specific molecular targets. In this work, novel oxazolo[5,4-d]pyrimidine derivatives were designed, synthesized, and evaluated in vitro for their cytotoxic activity against a panel of four human cancer cell lines (lung carcinoma: A549, breast adenocarcinoma: MCF7, metastatic colon adenocarcinoma: LoVo, primary colon adenocarcinoma: HT29), along with their P-glycoprotein-inhibitory ability and pro-apoptotic activity. These oxazolo[5,4-d]pyrimidine derivatives, which are structurally similar to nucleic purine bases in general, are characterized by the presence of a pharmacologically favorable isoxazole substituent at position 2...
Synthesis and biological potentials of some new 1,3,4-oxadiazole analogues
Medicinal Chemistry Research, 2017
In continuation of our research to explore new antiproliferative agents, we report herein the synthesis and antiproliferative activity of two new series of N-(substituted phenyl)-5-aryl-1,3,4-oxadiazol-2-amine (4a-j) and N-{[5aryl-1,3,4-oxadiazol-2-yl]methyl}-substituted aniline (4k-t) analogs. The antiproliferative activity of fifteen compounds (4a-h, and 4n) was tested against nine different panels of nearly 60 NCI human cancer cell lines. N-(2-Methoxyphenyl)-5-(4-chlorophenyl)-1,3,4-oxadiazol-2-amine (4b) and 4-{5-[(2-Methoxyphenyl)amino]-1,3,4-oxadiazol-2-yl} phenol (4c) showed maximum antiproliferative activity among the series with a mean growth percents (GPs) of 45.20 and 56.73, respectively. The compound 4b showed significant percent growth inhibitions (GIs) on nearly 47 cancer cell lines and were found to have higher sensitivity towards HL-60(TB), MDA-MB-435, OVCAR-3, and K-562 with percent GIs (GIs) of 109.62, 105.90, 91.94, and 88.30, respectively. Similarly the compound, 4c showed significant percent GIs on nearly 42 cancer cell lines and were found to have higher sensitivity towards UO-31, MDA-MB-435, KM12, and K-562 with %GIs of 84.31, 80.52, 78.65, and 77.06, respectively. Both the compounds 4b and 4c showed better antiproliferative activity than the standard drug Imatinib while the antiproliferative activity of compound 4b was found to be nearly comparable to the standard drug 5-flurouracil (5-FU). The antiproliferative activity of five compounds (4o-s) was tested against the breast cancer cell lines (MCF-7 and MDA-MB-231) as per Sulforhodamine B assay (SRB assay). N-{[5-(4-Methoxyphenyl)-1,3,4-oxadiazol-2-yl]methyl}-4-methylaniline (4p) was found to have significant antiproliferative activity against MCF-7 and MDA-MB-231 with GI 50 of 12.9 and 59.3 µM, respectively. Further, the free radical scavenging activity results were significant for the most active compounds, 4b (IC 50 = 21.07 µM) and 4c (IC 50 = 15.58 µM). The docking studies was also carried against tubulin enzyme and the most active compound (4b) showed good interaction with the residues Lys254, Ala250, Cys241, Val318, Ala316, Asn258, and Lys352 present in the hydrophobic cavity of tubulin.
Evaluation of anticancer activity of some 1,3,4-oxadiazole derivatives
Carboxymethyl derivatives of various para substituted/unsubstituted oxadiazole-2-thione have been evaluated for their potential anticancer activity. Male Swiss albino mice have been used as test animal. The anti-cancer activity has been evaluated by comparing the ability of the test compound (25 mg/kg) to inhibit the tumor weight as well as tumor cell count with that of the control. The results suggest that all the studied compounds show significant reduction in both tumor weight and tumor cell count with respect to that of the control. Compound 3 is found to the most potent. The standard compound used is Mitomycin C (1mg/kg).
Journal of Molecular Structure, 2023
New potential bioactive oxazolopyrimidines have been synthesized using two main approaches: the pyrimidine ring annulation on a functionalized oxazole and the benzoyl bromide trimerization followed by rearrangement and formation of the oxazolo[5,4-d]pyrimidine scaffold. The docking analyzes have shown that 7-piperazine substituted oxazolo[4,5-d]pyrimidines 8a-c could be potential VEGFR2 inhibitors with high free energy of ligand-protein complex formation (ΔG:-10.1,-9.6,-9.8 kcal/mol, respectively). In vitro antitumor assays confirmed theoretical predictions that oxazolo[4,5-d]pyrimidines 8a-c containing positively charged piperazine moiety should demonstrate significantly higher cytotoxic effects. 5-(4-Chlorophenyl)-2-phenyl-oxazolo[4,5d]pyrimidin-7-yl)-piperazin-1-ium trifluoroacetate 8c exhibited a slightly higher antiproliferative effect (IC50 = 0.21 µM) than doxorubicin (IC50 = 0.36 µM) on MDA-MB-231 cell line and has relatively good results on OVCAR-3 (IC50 = 1.7 µM) and HCT-116 (IC50 = 0.24 µM) cells.
Synthesis and antitumor activity of novel pyrazolo[3,4-d]pyrimidin-4(5H)-one derivatives
Starting from pyrazolo [3,4-d]pyrimidine ethyl ester 4 and its corresponding acid hydrazide 5, several new compounds were synthesized such as schiff bases 6a-e, acetyl azide derivative 7, phthalimido derivatives 8, compounds containing oxadiazole ring 9,10a-c, triazole ring system 11, 14,15, thiadiazole moiety 13 and phenyl thiosemicarbazide part 12. Some of the synthesized compounds were screened for their antitumor activity against human breast adenocarcinoma cell line (MCF-7) using doxorubicin as a positive control. Compounds 6d, 10b, 12 were found to exhibit good cytotoxic activity with IC50 equal to (4.6, 4.6,.8 µg/mL), respectively.
Anticancer activities of some newly synthesized pyrazole and pyrimidine derivatives
Archives of Pharmacal Research, 2013
A series of pyridine, pyrane, and pyrimidine derivatives (2-11) were newly synthesized using nitrobenzosuberone 1 as a starting material. The antitumor activities of the synthesized compounds were evaluated utilizing 59 different human tumor cell lines, representing leukemia, melanoma, lung, colon, brain, ovary, breast, prostate as well as kidney. Some of the tested compounds especially 2, 3, 4c, 6, 7, 9b, 10a, and 11 exhibited better in vitro antitumor activities at low concentration (log 10 GI 50 = À4.7) against the used human tumor cell lines. Additionally, compounds 3, 4c, 6, 7, and 9b were highly selective to inhibit leukemia cell lines. The detailed synthesis, spectroscopic data and antitumor properties for the synthesized compounds were reported.
International Journal of Pharmaceutical Sciences and Drug Research, 2018
Neoplasia is a type of abnormal and excessive growth of tissue. The growth of a neoplasia is uncoordinated with that of the normal surrounding tissue, and it persists growing abnormally, even if the original trigger is removed. This abnormal growth usually forms a mass. The main objective of the present research work was the synthesis, characterization and evaluation of in vivo antitumour activity of some novel 2, 5-disubstituted 1, 3, 4-oxadiazole derivatives. The in vivo antitumour activity of synthesized compounds was evaluated by HT 29 cell line induced malignant ascites on mouse model. The apoptosis of HT 29 cells was evaluated by using Gimsa and H33342 stain and the apoptosis ratios were analysed by FCM using AnnexinV-FITC/PI staining. The present experimental data displayed that the mortality was less in all groups except in tumour control group and all the synthesized compounds AB1-AB8 (100 mg/kg) significantly increased the PILS. While 5-FU increased the life span of 97.72%...
Open Journal of Medicinal Chemistry, 2017
A new series of 3-(methylthio)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidine derivatives was synthesized. The structures of the new derivatives were confirmed by the spectral data and elemental analyses. The antitumor activity of this series against human breast adenocarcinoma cell line MCF7 was evaluated. Out of twenty new derivatives, ten were revealed mild to moderate activity compared with doxorubicin as a reference antitumor. Among this new series N-(2-chlorophenyl)-2-(3-(methylthio)-4-oxo-1-phenyl-1H-pyrazolo[3,4-d]py rimidin-5(4H)-yl)acetamide (13 a) was found the most active one with IC 50 equal to 23 µM.