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Two well\u2010known targeting peptide sequences, RGD and NGR, were conjugated with naproxen and ibuprofen. It is expected that the RGD peptide selectively binds to \u03b1<jats:sub>v<\/jats:sub>\u2010integrin receptors, which are highly expressed in cancer cells, and that the NGR peptide selectively targets aminopeptidase N (APN\/CD13, EC 3.4.11.2), which is overexpressed in blood vessels of tumors. To investigate the impact of possible steric hindrance due to the attachment of the drug to the peptide, a linear six\u2010carbon linker (hexanoic acid) was also used as a spacer. Cytotoxic effects of the synthesized compounds were evaluated against several cancer cell lines, including MCF\u20107, A2780 (\u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub> positive), OVCAR3 (high \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>), HT\u20101\u201080, and SKOV\u20103 cells (CD13 positive). The NGR conjugate forms of both ibuprofen and naproxen showed better activity against the SKOV\u20103 tumor cell line. The improved binding of these conjugates to their receptors was confirmed by docking studies.<\/jats:p>","DOI":"10.1002\/ardp.201800379","type":"journal-article","created":{"date-parts":[[2019,7,18]],"date-time":"2019-07-18T11:39:39Z","timestamp":1563449979000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Design, synthesis and biological evaluation of peptide\u2010NSAID conjugates for targeted cancer therapy"],"prefix":"10.1002","volume":"352","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0143-0972","authenticated-orcid":false,"given":"Bahareh","family":"Shokri","sequence":"first","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2477-9533","authenticated-orcid":false,"given":"Afshin","family":"Zarghi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soraya","family":"Shahhoseini","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Mohammadi","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Farzad","family":"Kobarfard","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shahid Beheshti University of Medical Sciences  Tehran Iran"},{"name":"Phytochemistry Research Center Shahid Beheshti University of Medical Sciences  Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,7,18]]},"reference":[{"key":"e_1_2_6_1_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/35025220"},{"key":"e_1_2_6_1_2_2","doi-asserted-by":"publisher","DOI":"10.1038\/35025215"},{"key":"e_1_2_6_1_3_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020312220968"},{"key":"e_1_2_6_1_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(92)90115-S"},{"key":"e_1_2_6_1_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(02)00971-6"},{"key":"e_1_2_6_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1174"},{"key":"e_1_2_6_1_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0902-918"},{"key":"e_1_2_6_1_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0962-8924(99)01667-0"},{"key":"e_1_2_6_1_7_3","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.00071"},{"key":"e_1_2_6_1_7_4","doi-asserted-by":"publisher","DOI":"10.1016\/S0955-0674(96)80115-3"},{"key":"e_1_2_6_1_7_5","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(94)90007-8"},{"key":"e_1_2_6_1_8_1","doi-asserted-by":"publisher","DOI":"10.1089\/108497801300189218"},{"key":"e_1_2_6_1_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/newbio231232a0"},{"key":"e_1_2_6_1_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s000110050284"},{"key":"e_1_2_6_1_10_1","first-page":"18","author":"Williams C. 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