{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T10:46:01Z","timestamp":1780569961490,"version":"3.54.1"},"reference-count":78,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,14]],"date-time":"2022-11-14T00:00:00Z","timestamp":1668384000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Toledo and Centre of Medical"},{"name":"Bio-allied Health Sciences Research"},{"name":"Ajman University"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>In men, prostate cancer (PC) is the most frequently diagnosed cancer, causing an estimated 375,000 deaths globally. Currently, existing therapies for the treatment of PC, notably metastatic cases, have limited efficacy due to drug resistance and problematic adverse effects. Therefore, it is imperative to discover and develop novel drugs for treating PC that are efficacious and do not produce intolerable adverse or toxic effects. Condensed quinolines are naturally occurring anticancer compounds. In this study, we determined the in vitro efficacy of IND-2 (4-chloro-2-methylpyrimido[1\u2033,2\u2033:1,5]pyrazolo[3,4-b]quinolone) in the PC lines, PC-3 and DU-145. IND-2 significantly inhibited the proliferation of PC-3 and DU-145, with IC50 values of 3 \u00b5M and 3.5 \u00b5M, respectively. The incubation of PC-3 cells with 5 and 10 \u00b5M of IND-2 caused the loss of the mitochondrial membrane potential in PC-3 cells. Furthermore, IND-2, at 5 \u00b5M, increased the expression of cleaved caspase-3, cleaved caspase-7 and cleaved poly (ADP-ribose) polymerase (PARP). The incubation of PC-3 cells with 5 \u00b5M of IND-2 significantly decreased the expression of the apoptotic protein, B-cell lymphoma 2 (Bcl-2). Furthermore, 5 and 10 \u00b5M of IND-2 produced morphological changes in PC-3 cells characteristic of apoptosis. Interestingly, IND-2 (2.5, 5 and 10 \u00b5M) also induced mitotic catastrophe in PC-3 cells, characterized by the accumulation of multinuclei. The incubation of DU-145 cells with 1.25 and 5 \u03bcM of IND-2 significantly increased the levels of reactive oxygen species (ROS). Finally, IND-2, at 10 \u03bcM, inhibited the catalytic activity of topoisomerase II\u03b1. Overall, our findings suggest that IND-2 could be a potential lead compound for the development of more efficacious compounds for the treatment of PC.<\/jats:p>","DOI":"10.3390\/life12111879","type":"journal-article","created":{"date-parts":[[2022,11,15]],"date-time":"2022-11-15T02:28:58Z","timestamp":1668479338000},"page":"1879","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["IND-2, a Quinoline Derivative, Inhibits the Proliferation of Prostate Cancer Cells by Inducing Oxidative Stress, Apoptosis and Inhibiting Topoisomerase II"],"prefix":"10.3390","volume":"12","author":[{"given":"Swapnaa","family":"Balaji","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rabin","family":"Neupane","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saloni","family":"Malla","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul","family":"Khupse","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy, University of Findlay, Findlay, OH 43551, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haneen","family":"Amawi","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"},{"name":"Department of Pharmacy Practice, Faculty of Pharmacy, Yarmouk University, P.O. Box 566, Irbid 21163, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6994-0322","authenticated-orcid":false,"given":"Shikha","family":"Kumari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9503-3424","authenticated-orcid":false,"given":"Diwakar Bastihalli","family":"Tukaramrao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srestha","family":"Chattopadhyay","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Charles R.","family":"Ashby","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, College of Pharmacy & Pharmaceutical Sciences, St. John\u2019s University, New York, NY 11432, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2513-5879","authenticated-orcid":false,"given":"Sai H. S.","family":"Boddu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Health Sciences, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chandrabose","family":"Karthikeyan","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Indira Gandhi National Tribal University, Lalpur, Amarkantak 484887, Madhya Pradesh, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piyush","family":"Trivedi","sequence":"additional","affiliation":[{"name":"Center for Innovation and Translational Research, Poona College of Pharmacy, Bharati Vidyapeeth, Pune 411038, Maharashtra, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9340-1844","authenticated-orcid":false,"given":"Dayanidhi","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7427-7155","authenticated-orcid":false,"given":"Amit K.","family":"Tiwari","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Experimental Therapeutics, College of Pharmacy & Pharmaceutical Sciences, University of Toledo, Toledo, OH 43614, USA"},{"name":"Centre of Medical and Bio-allied Health Sciences Research, Ajman University, Ajman P.O. Box 346, United Arab Emirates"},{"name":"Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo, Toledo, OH 43614, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"a030361","DOI":"10.1101\/cshperspect.a030361","article-title":"The Epidemiology of Prostate Cancer","volume":"8","author":"Pernar","year":"2018","journal-title":"Cold Spring Harb. Perspect. 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