Cytotoxic Potential of Novel Quinoline Derivative: 11-(1,4-Bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline against Different Cancer Cell Lines via Activation and Deactivation of the Expression of Some Proteins
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Published:2023-09-20
Issue:18
Volume:24
Page:14336
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Abd Elrahman Sara Fathy1, Ahmed Abdullah A. S.1ORCID, Abd Elsatar Doaa1, Elkady Salma1, Elgendy Amira1, Alnakeeb Fatma1ORCID, Elmongy Elshaymaa I.2ORCID, Henidi Hanan A.3ORCID, El-Gendy Saad M.4, El Sayed Ibrahim El Tantawy1, El-Gokha Ahmed A.1, Abd Eldaim Mabrouk Attia5ORCID
Affiliation:
1. Department of Chemistry, Faculty of Science, Menoufia University, Shibin El-Kom 32511, Egypt 2. Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Helwan University, Cairo 11795, Egypt 3. Research Department, Health Sciences Research Center, Princess Nourah bint Abdulrahman University, Riyadh 84428, Saudi Arabia 4. Department of Cancer Biology, National Cancer Institute, Cairo University, Cairo 11562, Egypt 5. Department of Biochemistry and Chemistry of Nutrition, Faculty of Veterinary Medicine, Menoufia University, Shibin El-Kom 32511, Egypt
Abstract
The current study evaluated the cytotoxic activity of 11-(1,4-bisaminopropylpiperazinyl)5-methyl-5H-indolo[2,3-b]quinoline (BAPPN), a novel derivative of 5-methyl-5H-indolo[2,3-b]quinoline, against hepatocellular carcinoma (HepG2), colon carcinoma (HCT-116), breast (MCF-7), and lung (A549) cancer cell lines and the possible molecular mechanism through which it exerts its cytotoxic activity. BAPPN was synthesized and characterized with FT-IR and NMR spectroscopy. The binding affinity scores of BAPPN for caspase-3 PDB: 7JL7 was −7.836, with an RMSD of 1.483° A. In silico screening of ADME properties indicated that BAPPN showed promising oral bioavailability records in addition to their high gastrointestinal absorption and blood–brain barrier penetrability. BAPPN induced cytotoxicity, with IC50 values of 3.3, 23, 3.1, and 9.96 μg/mL against cancer cells HepG2, HCT-116, MCF-7, and A549, respectively. In addition, it induced cell injury and morphological changes in ultracellular structure, including cellular delayed activity, vanishing of membrane blebbing, microvilli, cytoplasmic condensation, and shrunken nucleus with more condensed chromatin autophagosomes. Furthermore, BAPPN significantly increased the protein expression of caspase-3 and tumor suppressor protein (P53). However, it significantly reduced the secretion of vascular endothelial growth factor (VEGF) protein into the medium and decreased the protein expression of proliferation cellular nuclear antigen (PCNA) and Ki67 in HepG2, HCT-116, MCF-7, and A549 cells. This study indicates that BAPPN has cytotoxic action against liver, colon, breast, and lung cancer cell lines via the up-regulation of apoptotic proteins, caspase-3 and P53, and the downregulation of proliferative proteins, VEGF, PCNA, and Ki67.
Funder
Deanship of Scientific Research at Princess Nourah bint Abdulrahman University
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
Cited by
1 articles.
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