Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity

Amit Tiwari, N. Gopalan Kutty, Nitesh Kumar, Anil Chaudhary, P. Vasanth Raj, Rekha Shenoy, C. Mallikarjuna Rao

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

Original languageEnglish
Pages (from-to)2553-2565
Number of pages13
JournalCytotechnology
Volume68
Issue number6
DOIs
Publication statusPublished - 01-12-2016

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Amikacin
Cytotoxicity
Tumors
Cells
Derivatives
Assays
Tumor Burden
Oxadiazoles
Neoplasms
DNA
Ladders
Staining and Labeling
Cell Line
Inhibitory Concentration 50
Artemia
Acridine Orange
Mitochondria
Ethidium
Propidium
DNA Fragmentation

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Bioengineering
  • Biomedical Engineering
  • Clinical Biochemistry
  • Cell Biology

Cite this

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title = "Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity",
abstract = "The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.",
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Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity. / Tiwari, Amit; Gopalan Kutty, N.; Kumar, Nitesh; Chaudhary, Anil; Vasanth Raj, P.; Shenoy, Rekha; Mallikarjuna Rao, C.

In: Cytotechnology, Vol. 68, No. 6, 01.12.2016, p. 2553-2565.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Synthesis and evaluation of selected 1,3,4-oxadiazole derivatives for in vitro cytotoxicity and in vivo anti-tumor activity

AU - Tiwari, Amit

AU - Gopalan Kutty, N.

AU - Kumar, Nitesh

AU - Chaudhary, Anil

AU - Vasanth Raj, P.

AU - Shenoy, Rekha

AU - Mallikarjuna Rao, C.

PY - 2016/12/1

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N2 - The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

AB - The oxadiazole moiety is known for its anticancer activity through its antiangiogenic and mitostatic potential. Taking this as a cue, the present study was designed to investigate the anti-cancer potential of selected oxadiazole derivatives. Twelve 1,3,4-oxadiazole derivatives (AMK OX-1 to AMK OX-12) were synthesized and were tested for IC50 values through brine shrimp lethality assay and MTT assay on HeLa and A549 cell lines. Four compounds, AMK OX-8, 9, 11 and 12 showed potential cytotoxicity activity with low IC50 value. These compounds produced considerable cytotoxic effect on Hep-2 and A549 cancer cell lines. However, they were found to be comparatively safer to normal cell lines, viz., V-79 cell lines than to the tested cancer cell lines, such as HeLa, A 549, and Hep2 cell lines. The mechanism of cytotoxicity was evaluated through nuclear staining and DNA ladder assay. Although DNA ladder assay showed DNA fragmentation (apoptotic phenomenon) in Hep-2 cells treated with only AMK OX-12, the staining procedures using acridine orange, ethidium bromide and propidium iodide showed apoptotic bodies in cells treated with AMK OX-8, 9 and 12 also. In JCI staining on isolated mitochondria of Hep2 cells, AMK OX-8, 9-11 and 12 displayed increasing fluorescence intensity with time which confirmed involvement of mitochondrial pathway and intrinsic pathway of apoptosis. All four compounds were found to be safe in acute oral toxicity study in Swiss albino mice. These derivatives were effective in reducing tumor size and weight in the in vivo DLA-induced solid tumor model. They were found to be significantly effective in reducing tumor volume and tumor weight.

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