Tanvi A. Desphande , Andi Zeng , Michelle Young , Terrence Nicholson , Karen Luo , Sudip Timilsina , Bryan Q. Spring , Peter Müller , Neha Kulkarni , Swati Betharia , Ronny Priefer
{"title":"Synthesis and evaluation of Aza-PLADIPYs: A novel class of cytotoxic agents","authors":"Tanvi A. Desphande , Andi Zeng , Michelle Young , Terrence Nicholson , Karen Luo , Sudip Timilsina , Bryan Q. Spring , Peter Müller , Neha Kulkarni , Swati Betharia , Ronny Priefer","doi":"10.1016/j.rechem.2025.102114","DOIUrl":null,"url":null,"abstract":"<div><div>A novel class of platinum containing anticancer agents, specifically aza‑platinum-dipyrromethenes (aza-PLADIPYs) has been developed and assessed. These were synthesized with the aim of being dual-acting anticancer agents, hypothesized to produce both DNA crosslinking chemotoxicity and phototoxicity. The aza-PLADIPYs displayed a distorted square planar structure, which unexpectedly included a Pt<img>C bond. We compared the activity of these agents to that of Photofrin® (a photodynamic therapy (PDT) agent) and cisplatin (a DNA crosslinking agent). These compounds did not exhibit any PDT activity. However, they demonstrated promising cytotoxicity against partial cisplatin-resistant human ovarian carcinoma (OVCAR5) cells. Among the tested compounds, Compound <strong>4</strong> (R = OCH<sub>3</sub>) exhibited the highest cytotoxicity, achieving approximately 78 % cell death at 250 μM, which is significantly higher than the 54 % cell death observed with cisplatin at the same concentration. Impressively, the aza-PLADIPYs displayed virtually no nephrotoxicity at concentrations up to 250 μM, when tested on HK-2 kidney proximal tubule cells, overcoming one of the major dose-limiting side effects of platinum containing anticancer agents.</div></div>","PeriodicalId":420,"journal":{"name":"Results in Chemistry","volume":"14 ","pages":"Article 102114"},"PeriodicalIF":4.2000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Results in Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2211715625000979","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/2/13 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
A novel class of platinum containing anticancer agents, specifically aza‑platinum-dipyrromethenes (aza-PLADIPYs) has been developed and assessed. These were synthesized with the aim of being dual-acting anticancer agents, hypothesized to produce both DNA crosslinking chemotoxicity and phototoxicity. The aza-PLADIPYs displayed a distorted square planar structure, which unexpectedly included a PtC bond. We compared the activity of these agents to that of Photofrin® (a photodynamic therapy (PDT) agent) and cisplatin (a DNA crosslinking agent). These compounds did not exhibit any PDT activity. However, they demonstrated promising cytotoxicity against partial cisplatin-resistant human ovarian carcinoma (OVCAR5) cells. Among the tested compounds, Compound 4 (R = OCH3) exhibited the highest cytotoxicity, achieving approximately 78 % cell death at 250 μM, which is significantly higher than the 54 % cell death observed with cisplatin at the same concentration. Impressively, the aza-PLADIPYs displayed virtually no nephrotoxicity at concentrations up to 250 μM, when tested on HK-2 kidney proximal tubule cells, overcoming one of the major dose-limiting side effects of platinum containing anticancer agents.
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