Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

doi:10.1186/s13065-021-00757-y

. 2021 May 4;15(1):30.

doi: 10.1186/s13065-021-00757-y.

Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

Ravi Kumar Bommera¹, Shashikala Kethireddy², Rajeshwar Reddy Govindapur³, Laxminarayana Eppakayala⁴

Affiliations

¹ Sreenidhi Institute of Science and Technology (Autonomous), Yamnampet, Ghatkesar, Hyderabad, Telangana, India.
² Geethanjali College of Engineering and Technology, (Autonomous), Cheeryal, Keesara, Hyderabad, Telangana, India.
³ University of North Carolina Wilmington, Wilmington, NC, 28409, USA.
⁴ Sreenidhi Institute of Science and Technology (Autonomous), Yamnampet, Ghatkesar, Hyderabad, Telangana, India. elxnkits@yahoo.co.in.

PMID: 33947440
PMCID: PMC8097950
DOI: 10.1186/s13065-021-00757-y

Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

Ravi Kumar Bommera et al. BMC Chem. 2021.

. 2021 May 4;15(1):30.

doi: 10.1186/s13065-021-00757-y.

Authors

Ravi Kumar Bommera¹, Shashikala Kethireddy², Rajeshwar Reddy Govindapur³, Laxminarayana Eppakayala⁴

Affiliations

¹ Sreenidhi Institute of Science and Technology (Autonomous), Yamnampet, Ghatkesar, Hyderabad, Telangana, India.
² Geethanjali College of Engineering and Technology, (Autonomous), Cheeryal, Keesara, Hyderabad, Telangana, India.
³ University of North Carolina Wilmington, Wilmington, NC, 28409, USA.
⁴ Sreenidhi Institute of Science and Technology (Autonomous), Yamnampet, Ghatkesar, Hyderabad, Telangana, India. elxnkits@yahoo.co.in.

PMID: 33947440
PMCID: PMC8097950
DOI: 10.1186/s13065-021-00757-y

Abstract

Background: 1,2,4-oxadiazole derivatives exhibited significant anti-cancer activity when they were evaluated, against human cancer cell lines. They also showed anti-inflammatory, analgesic, diabetic, immunosuppressive, α,β₃-receptor antagonist, antimicrobial, anti-helminthic, histamine-H3 and antiparasitic properties. A pyrimidine analog, 5 fluoro-uracil is a chemotherapeutic drug used for treating multiple solid malignant tumors. But its application is limited, as it has side effects like low bioavailability and high toxicity. Molecular docking is an exemplary tool, helps in identifying _target and designing a drug containing high bio-availability and minimum toxicity.

Results: A set of 1,2,4-oxadiazole linked 5-fluoruracil derivatives (7a-j) were synthesized and their structures were confirmed by ¹HNMR, ¹³CNMR and Mass spectral analysis. Further, these compounds were investigated for their anticancer activity towards a panel of four human cancer cell lines such as (MCF-7, MDA MB-231), lung cancer (A549) and prostate cancer (DU-145) by using MTT method. Among them, compounds 7a, 7b, 7c, 7d and 7i demonstrated more promising anticancer activity than standard.

Conclusion: Synthesized derivatives (7a-j) of 1,2,4-oxadiazole linked 5-fluorouracil and investigated for their anticancer activity towards a panel of four human cancer cell lines.

Keywords: 5-Fluorouracil; Ataluren; Oxadiazole and anticancer activity; Pyrimidine.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

**Fig. 1**
(1) 5-Fluoro uracil, (2) ataluren

**Fig. 2**
3D and 2D interactions of co-crystal ligand with VEGFR protein (PDB ID: 1YWN)

**Fig. 3**
3D and 2D interactions of 7j with VEGFR protein (PDB ID: 1YWN)

**Fig. 4**
3D and 2D interactions of 7h with VEGFR protein (PDB ID: 1YWN)

**Fig. 5**
Pharmacophore feature generation by using PharmaGist webserver of all ligands

**Fig. 6**
3DPlot of in silico ADMET prediction

See this image and copyright information in PMC

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[1] Ghomi JS, Ghasemzadeh MA. An efficient route to the synthesis of pyrimidine-2-ones under ultrasound irradiation. Dig J Nanomater Biostruct. 2010;5:303–306.

[2] Ghomi JS, Ghasemzadeh MA. An efficient route to the synthesis of pyrimidine-2-ones under ultrasound irradiation. Dig J Nanomater Biostruct. 2010;5:303–306.

[3] Wagner E, Al-Kadasi K, Zimecki M, Sawka-Dobrowolska W. Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine. Eur J Med Chem. 2008;43:2498–2504. doi: 10.1016/j.ejmech.2008.01.035. - DOI - PubMed

[4] Wagner E, Al-Kadasi K, Zimecki M, Sawka-Dobrowolska W. Synthesis and pharmacological screening of derivatives of isoxazolo[4,5-d]pyrimidine. Eur J Med Chem. 2008;43:2498–2504. doi: 10.1016/j.ejmech.2008.01.035. - DOI - PubMed

[5] Ukrainets IV, Tugaibei IA, Bereznykova NL, Karvechenko VN, Turov AV. 4-Hydroxy-2-quinolones 144. Alkyl-, arylalkyl- and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid and their diuretic properties. Chem Heterocycl Compd. 2008;5:565–575. doi: 10.1007/s10593-008-0076-7. - DOI

[6] Ukrainets IV, Tugaibei IA, Bereznykova NL, Karvechenko VN, Turov AV. 4-Hydroxy-2-quinolones 144. Alkyl-, arylalkyl- and arylamides of 2-hydroxy-4-oxo-4H-pyrido[1,2-a]pyrimidine-3-carboxylic acid and their diuretic properties. Chem Heterocycl Compd. 2008;5:565–575. doi: 10.1007/s10593-008-0076-7. - DOI

[7] Ballell L, Field RA, Chung GAC, Young RJ. New thio pyrazolo [3, 4-d] pyrimidine derivatives as anti-mycobacterial agents. Bioorg Med Chem Lett. 2007;17:1736–1740. doi: 10.1016/j.bmcl.2006.12.066. - DOI - PubMed

[8] Ballell L, Field RA, Chung GAC, Young RJ. New thio pyrazolo [3, 4-d] pyrimidine derivatives as anti-mycobacterial agents. Bioorg Med Chem Lett. 2007;17:1736–1740. doi: 10.1016/j.bmcl.2006.12.066. - DOI - PubMed

[9] Fujiwara N, Nakajima T, Ueda Y, Fujita H, Kawakami H. Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation. Bioorg Med Chem. 2008;16:9804–9816. doi: 10.1016/j.bmc.2008.09.059. - DOI - PubMed

[10] Fujiwara N, Nakajima T, Ueda Y, Fujita H, Kawakami H. Novel piperidinylpyrimidine derivatives as inhibitors of HIV-1 LTR activation. Bioorg Med Chem. 2008;16:9804–9816. doi: 10.1016/j.bmc.2008.09.059. - DOI - PubMed

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Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

Affiliations

Synthesis, biological evaluation and docking studies of 1,2,4-oxadiazole linked 5-fluorouracil derivatives as anticancer agents

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Abstract

Conflict of interest statement

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Abstract

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