Synthesis of Novel Hybrids Inspired from Bromopyrrole Alkaloids Inhibiting MMP‐2 and ‐12 as Antineoplastic Agents. (30th December 2014)

• Record Type: Journal Article
• Authors: Rane, Rajesh A.; Naphade, Shital S.; Bangalore, Pavan Kumar; Palkar, Mahesh B.; Patel, Harun M.; Shaikh, Mahamadhanif S.; Alwan, Wesam S.; Karpoormath, Rajshekhar
• Is Part Of: Chemical biology & drug design. Volume 86:Number 2(2015:Aug.)
• Page Start: 210
• Page End: 222
• Publication Date: 2014-12-30
• Subjects: Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.12481
• Languages: English
• ISSNs: 1747-0277

Abstract

<abstract abstract-type="main" id="cbdd12481-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <p>Synthesis of novel set of forty semicarbazide/thiosemicarbazide hybrids inspired from marine bromopyrrole alkaloids is reported. Biological screening of these hybrids against a panel of five human cancer cell lines identified a number of hits endowed with interesting cytotoxicity profile. Compounds <bold>5c</bold> and <bold>5e</bold> (IC<sub>50</sub> = 0.03 <italic>μ</italic><sc>m</sc>), <bold>5t</bold> (IC<sub>50</sub> = 0.03 <italic>μ</italic><sc>m</sc>), <bold>4s</bold> (IC<sub>50</sub> = 0.07 <italic>μ</italic><sc>m</sc>), and <bold>5n</bold> (IC<sub>50</sub> = 0.01 <italic>μ</italic><sc>m</sc>) displayed maximum cytotoxicity toward hormone‐dependent breast cancer cells <bold>MCF</bold><bold>7</bold>, hepatic cancer cells <bold>WRL</bold><bold>68</bold>, colon cancer cells <bold>Ca</bold><bold>CO</bold><bold>2</bold> and mouth and oral cancer cells <bold>KB</bold><bold>403</bold>, respectively. The most active hits were further investigated for their potential to inhibit MMP‐2 and MMP‐12. Compound <bold>5e</bold> showed maximum activity (IC<sub>50</sub> = 1.8 <italic>μ</italic><sc>m</sc>) toward MMP‐2. Further, we preformed anti‐invasive assay on the most active compounds, where <bold>Ca</bold><bold>CO</bold><bold>2</bold> tumor cell migration was significantly decreased (77.9%) by hybrid <bold>5e</bold>. The non‐toxicity toward human VERO cells (IC<sub>50</sub> = 83.1 to 231.8 <italic>μ</italic><sc>m</sc>) indicated the selectivity of most active hits (<bold>5c</bold>, <bold> 5e</bold>, <bold> 5t</bold> and <bold>5n</bold>) toward cancer cells.</p> </abstract>