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Similar to BH3 mimetics, targeting the antiapoptotic Bcl\u2010xL:Beclin1 protein complex is crucial to inducing apoptosis and autophagy, thereby suppressing tumor progression in breast cancer cells. This study aims to synthesize and evaluate a series of imidazopyridine\u2010tethered pyrazoline drug prejudice\u2010scaffold derivatives (5a\u20105l) as Beclin\u20101 mimetics that induce apoptosis and autophagy and mainly for their potential anticancer activity, focusing on the most potent compound 5c. The primary goal is to assess its ability of compound 5c to inhibit Bcl\u2010xL:Beclin\u20101 interaction, thereby inducing a protective autophagic response subsequently to assess apoptosis to suppress breast cancer cell proliferation. Molecular docking studies were conducted to evaluate the binding affinity of compound 5c with Bcl\u2010xL, and the interactions were visualized through a three\u2010dimensional interaction map, highlighting key stabilizing interactions. Cytotoxic effects of compound 5c on MCF\u20107 breast cancer cells were assessed using alamarblue assay. To investigate the antiproliferative potential, colony formation, and wound healing assays were performed at varying concentrations. Apoptotic induction was analyzed through Western blotting for key proteins (BAX, Bcl\u2010xL, Bcl\u20102), caspase\u20103\/7 activation, and AnnexinV\/PI assay using flow cytometry. Additionally, autophagy was examined by monitoring LC3B\u2010I to LC3B\u2010II conversion, Beclin\u20101 upregulation, and lysosomal activity using LysoTrackerRed staining. The involvement of compound 5c in autophagic flux was further confirmed by quantifying LC3\u2010II accumulation in the presence of an autophagy inhibitor chloroquine (CQ), and then the effect of 5c\u2010induced cell viability and apoptosis were evaluated and caspase\u20103\/7 activity, respectively, during autophagy inhibition condition in MCF\u20107 cell line. A strong binding interaction of compound 5c with the hydrophobic groove of Bcl\u2010xL demonstrated its potential as an effective Bcl\u2010xL inhibitor. Compound 5c significantly reduced MCF\u20107 cell viability in a dose\u2010dependent manner (IC50: 9.7\u2009\u03bcM). The inhibitory effect of compound 5c on cancer cell proliferation and migration was observed. Treatment with compound 5c induced dose\u2010dependent apoptosis in MCF\u20107 cells, as confirmed by Annexin V\/PI using flow cytometric analysis after 72\u2009h of exposure. A significant decrease in viable cells accompanied by an increase in apoptotic cell populations was observed with increasing concentrations of 5c. Upregulated BAX expression and downregulation in Bcl\u2010xL and Bcl\u20102 expression levels indicated apoptosis induction. Caspase\u20103\/7 activation further confirmed apoptotic cell death. Autophagy assessment revealed enhanced LC3B\u2010II accumulation, Beclin\u20101 upregulation, and reduced p62 levels, suggesting modulation of autophagy. CQ treatment further increased LC3\u2010II levels, indicating compound 5c\u2010mediated autophagic flux induction and a significant reduction in cell viability and increased caspase 3\/7 activity, confirming modultion of autophagy\u2010dependent apoptosis by 5c. Similar to BH3 mimetic, compound 5c emerges as a promising small\u2010molecule inhibitor targeting the Bcl\u2010xL:Beclin\u20101 complex, which effectively induces apoptosis by modulating protective autophagy in breast cancer cells. Its dual mechanism of action highlights its potential as a novel therapeutic candidate for breast cancer treatment.<\/jats:p>","DOI":"10.1111\/cbdd.70287","type":"journal-article","created":{"date-parts":[[2026,4,17]],"date-time":"2026-04-17T12:30:14Z","timestamp":1776429014000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pyrazoline\u2013Imidazopyridine Hybrids as Beclin\u20101 Mimetics Driving Dual Apoptotic and Autophagy in Breast Cancer"],"prefix":"10.1111","volume":"107","author":[{"given":"Rashmi","family":"Shivakumar","sequence":"first","affiliation":[{"name":"Laboratory of Chemical Biology, Department of Studies in Organic Chemistry University of Mysore  Mysore Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Narasimha M.","family":"Beeraka","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Histology I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University)  Moscow Russia"},{"name":"Saveetha Institute of Basic Medical Sciences (SIBMS) Saveetha Institute of Medical and Technical Sciences Saveetha University  Chennai Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riyaz Ali M.","family":"Osmani","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutics College of Pharmacy, King Khalid University (KKU)  Al Faraa Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bhoomika B.","family":"Ravi","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Department of Studies in Organic Chemistry University of Mysore  Mysore Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Monisha H. S.","family":"Yadhav","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Department of Studies in Organic Chemistry University of Mysore  Mysore Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dileep","family":"Nagaraju","sequence":"additional","affiliation":[{"name":"Laboratory of Chemical Biology, Department of Studies in Organic Chemistry University of Mysore  Mysore Karnataka India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chandra Sekhar","family":"Bhol","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Yong Loo Lin School of Medicine National University of Singapore  Singapore Singapore"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Allaka","family":"Nagalakshmi","sequence":"additional","affiliation":[{"name":"Department of Molecular Diagnostics and Vaccines SYENICA Biotech Limited  Chennai Tamil Nadu India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2882-0612","authenticated-orcid":false,"given":"Kwang Seok","family":"Ahn","sequence":"additional","affiliation":[{"name":"Department of Science in Korean Medicine Kyung Hee University  Seoul Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-9957","authenticated-orcid":false,"given":"Vladimir N.","family":"Nikolenko","sequence":"additional","affiliation":[{"name":"Department of Human Anatomy and Histology I.M. 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