Novel 2-cyanoacrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene derivatives as potent anticancer agents
Corresponding Author
Farid M. Sroor
Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorMohamad M. Aboelenin
Cell Biology Department, National Research Centre, Dokki, Giza, Egypt
Search for more papers by this authorKarima F. Mahrous
Cell Biology Department, National Research Centre, Dokki, Giza, Egypt
Search for more papers by this authorKhaled Mahmoud
Pharmacognosy Department, National Research Centre, Dokki, Egypt
Search for more papers by this authorCorresponding Author
Ahmed H. M. Elwahy
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorCorresponding Author
Ismail A. Abdelhamid
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorCorresponding Author
Farid M. Sroor
Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorMohamad M. Aboelenin
Cell Biology Department, National Research Centre, Dokki, Giza, Egypt
Search for more papers by this authorKarima F. Mahrous
Cell Biology Department, National Research Centre, Dokki, Giza, Egypt
Search for more papers by this authorKhaled Mahmoud
Pharmacognosy Department, National Research Centre, Dokki, Egypt
Search for more papers by this authorCorresponding Author
Ahmed H. M. Elwahy
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorCorresponding Author
Ismail A. Abdelhamid
Chemistry Department, Faculty of Science, Cairo University, Giza, Egypt
Correspondence Farid M. Sroor, Organometallic and Organometalloid Chemistry Department, National Research Centre, Cairo 12622, Egypt.
Email: [email protected] and [email protected] (F. M. S.)
Ahmed H. M. Elwahy and Ismail A. Abdelhamid, Department of Chemistry, Faculty of Science, Cairo University, Giza 12613, Egypt.
Email: [email protected] (A. H. M. E.) and [email protected] (I. A. A.)
Search for more papers by this authorAbstract
Ethyl 2-acrylamido-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate as well as its corresponding bis-derivatives, 5–10, with aliphatic linkers were synthesized, fully characterized, and tested as novel anticancer agents. The targeted compounds, 5–10, were obtained by the Knoevenagel condensation reactions of bis-o- or -p-aldehyde with a molar ratio of ethyl 2-(2-cyanoacetamido)-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carboxylate of 2 in the presence of piperidine in excellent yields (93–98%). The in vitro anticancer activities of the prepared compounds were evaluated against HepG2, MCF-7, HCT-116, and BJ1 cells. Compounds 7 and 9 emerged as the most promising compounds, with IC50 values of 13.5 and 32.2 µg/ml, respectively, against HepG2 cells, compared with the reference drug doxorubicin (IC50: 21.6 µg/ml). Real-time reverse-transcription polymerase chain reaction was used to measure the changes in expression levels of the COL10A1 and COL11A1, ESR1, and ERBB2, or AXIN1 and CDKN2A genes within the treated cells, as genetic markers for colon, breast, or liver cancers, respectively. Treatment of the colon cancer cells with compounds 5, 9, and 10, or breast and liver cancers cells with compounds 7, 8, 9, and 10 downregulated the expression of the investigated tumor markers. The DNA damage values (depending on comet and DNA fragmentation assays) increased significantly upon treatment of colon cancer cells with compounds 5, 9, and 10, and breast and liver cells with compounds 8, 9, and 10. The structure–activity relationship suggested that the increase of the chain of the alkyl linker increases the anticancer activity and the compounds with bis-cyanoacrylamide moieties are more active than those with one cyanoacrylamide moiety.
Supporting Information
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