Synthesis, Characterization and Biological Evaluation of Some Novel 1,3,4-Oxadiazole Derivatives as Potential Anticancer Agents (original) (raw)
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Synthesis and Anticancer Evaluation of New 1,3,4-Oxadiazole Derivatives
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In order to develop novel chemotherapeutic agents with potent anticancer activities, a series of new 2,5-diaryl/heteroaryl-1,3,4-oxadiazoles were designed and synthesized. The structures of the new compounds were established using elemental analyses, IR and NMR spectral data. The compounds were evaluated for their anticancer potential on two standardized human cell lines, HT-29 (colon adenocarcinoma) and MDA-MB-231 (breast adenocarcinoma). Cytotoxicity was measured by MTS assay, while cell cycle arrest and apoptosis assays were conducted using a flow cytometer, the results showing that the cell line MDA-MB-231 is more sensitive to the compounds’ action. The results of the predictive studies using the PASS application and the structural similarity analysis indicated STAT3 and miR-21 as the most probable pharmacological targets for the new compounds. The promising effect of compound 3e, 2-[2-(phenylsulfanylmethyl)phenyl]-5-(4-pyridyl)-1,3,4-oxadiazole, especially on the MDA-MB-231 cel...
Synthesis of 1,2,4-oxadiazole derivatives: anticancer and 3D QSAR studies
Monatshefte für Chemie - Chemical Monthly, 2020
A 3D QSAR study was performed on 1,2,4-oxadiazole derivatives using the [(SW) kNN MFA], CoMFA, and CoMSIA techniques. On the basis of 3D QSAR outcomes, new molecules were designed by substituting different substituents. These designed compounds were synthesized and confirmed their synthesis by spectroscopic techniques. The synthesized compounds were screened for their anticancer activity against different cancer cell lines. Compound 2-[3-(pyridine-4-yl)-1,2,4oxadiazol-5-yl]benzo[d]thiazole showed equipotent (IC 50 = 4.96 μM) as 5-fluorouracil (IC 50 = 3.2 μM) against colon (CaCo-2) cancer cell line, and compound [2-[3-(pyridin-4-yl)-1,2,4-oxadiazol-5-yl]benzo[d]thiazol-4-yl]methanol showed equipotent activity (IC 50 = 0.35 μM) as compared to 5-fluorouracil (IC 50 = 0.23 μM) against colorectal (DLD1) cancer cell line. Compound 2-[3-(3,4-dimethoxyphenyl)-1,2,4-oxadiazol-5-yl]benzo[d]thiazole was found to be 4-5 less potent (IC 50 = 19.40 μM) as paclitaxel (IC 50 = 4.10 μM) against breast (T47D) cancer cell line, and compound 4-[5-(benzo[d]thiazol-2-yl)-1,2,4oxadiazol-3-yl]benzene-1,2-diol was found about 10 times less potent (IC 50 = 15.7 μM) than mitomycin (IC 50 = 1.50 μM) against prostate (PC-3) cancer cell line. These results disclose the discovery of new 1,2,4-oxadiazole-based anticancer drugs.
Design and Synthesis of Some New Oxadiazole Derivatives as Anticancer Agents
2022
In this work, some new oxadiazole derivatives have been prepared, by reacting phenyl hydrazine and acetic anhydride together, which furnished 2,4dimethyl-4-phenyloxadiazole. This product was reacted with a series of aromatic aldehydes, to obtain a series of oxadiazole derivatives. These derivatives were characterized by TLC, melting points, infrared red, proton nuclear magnetic resonance, carbon thirteen nuclear magnetic resonance and mass spectroscopy. Finally, these synthetized derivatives were tested for antiproliferative activity by two different cell lines. MCF-7 (Breast cancer cell line) and HepG2 (Liver cancer cell line) were used to assess the antiproliferative activity of the prepared compounds.
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%...
Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie, 2017
A series of new 1,3,4-oxadiazole-2(3H)-thione analogues (3a to 3o) have been designed, synthesized and evaluated for their anticancer activity. Four different cancerous cell lines viz. HeLa (cervical), U-87 (glioblastoma), Panc (pancreatic) and MCF-7 (breast) were used to assess the potency of the synthesized compounds as anticancer agents. Among them 3i and 3j showed promising cytotoxicity against HeLa cell line. Further, 3i and 3j successfully inhibited cell cycle progression and displayed cell death in HeLa cells via apoptosis as visualized by Annexin V APC and DNA fragmentation assay. 3i and 3j induced caspase-3 activation, PARP cleavage, increase in expression of proapoptotic protein Bax and decrease in the expression of antiapoptotic protein Bcl-2. Also, 3i and 3j induced overexpression of p21 and decreased expression of cyclin B1 indicating the arrest of cells in G2-M phase of the cell cycle. Therefore, new lead compounds are being suggested having anticancer activity through...
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).
Bioorganic & Medicinal Chemistry, 2006
A series of 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives was synthesized and 13 of them were selected by the National Cancer Institute (NCI) and evaluated for their in vitro anticancer activity. Seven of the investigated compounds, 3i, 3j, 3k, 3o, 3p, 3q, and 3r, displayed high anticancer activity in the primary assay. These compounds have been selected for a full anticancer screening against a 60-cell panel assay where they showed non-selective broad spectrum and promising activity against all cancer cell lines. Compounds 3j and 3k proved to be the active members in this study compared to 5-fluorouracil and cyclophosphamide as reference drugs, respectively. Compounds 3j and 3k were identified as promising lead compounds.A series of 5-(2-hydroxyphenyl)-3-substituted-2,3-dihydro-1,3,4-oxadiazole-2-thione derivatives was synthesized and tested for anticancer activity.
ChemInform, 2012
The synthetic strategies and characterization of some novel 1,3,4-oxadiazole derivatives carrying different pharmacophores and heterocyclic rings that are relevant to potential antitumor and cytotoxic activities are described. The antitumor activities of the newly synthesized compounds were evaluated according to the protocol of the National Cancer Institute (NCI) in-vitro disease-oriented human cells screening panel assay. The results revealed that five compounds, namely 2, 7a, 11a, 12b, and 17; displayed promising in-vitro antitumor activity in the 4-cell lines assay. Incorporating a thiazole ring to 1,3,4oxadiazole skeleton resulted in better antitumor activities than those displayed by the pyrazole and thiophene ring systems. Transformation of 1,3,4-oxadiazole 2 to N-(6-amino-7H-pyrazolo[5,1-c][1,2,4] triazol-3-yl)benzamide (15) diminished the antitumor activity.
Synthesis and antitumor evaluation of some new 1,3,4-oxadiazole-based heterocycles
European Journal of Medicinal Chemistry, 2012
The synthetic strategies and characterization of some novel 1,3,4-oxadiazole derivatives carrying different pharmacophores and heterocyclic rings that are relevant to potential antitumor and cytotoxic activities are described. The antitumor activities of the newly synthesized compounds were evaluated according to the protocol of the National Cancer Institute (NCI) in-vitro disease-oriented human cells screening panel assay. The results revealed that five compounds, namely 2, 7a, 11a, 12b, and 17; displayed promising in-vitro antitumor activity in the 4-cell lines assay. Incorporating a thiazole ring to 1,3,4oxadiazole skeleton resulted in better antitumor activities than those displayed by the pyrazole and thiophene ring systems. Transformation of 1,3,4-oxadiazole 2 to N-(6-amino-7H-pyrazolo[5,1-c][1,2,4] triazol-3-yl)benzamide (15) diminished the antitumor activity.