Synthesis of Oxadiazole–Morpholine derivatives and manifestation of the repressed CD31 Microvessel Density (MVD) as tumoral angiogenic parameters in Dalton’s Lymphoma - By Vigneshwaran V.

V. VIGNESHWARAN,

PhD Scholar, Kuvempu University

NOTE: THIS IS A RE-POST ADOPTED FROM THE WEBPAGE OF MOLECULAR BIOMEDICINE LABORATORY (MBL). Click here to view the original article 

                         Tumor tissues recruit the blood vessels and displays an enormous vasculature. This is in fact responsible for the tumors aggressiveness and metastasis. The evidence for the involvement of neovasculature in tumor progression and metastasis has been shown in numerous studies. Hence we have attempted to repress the tumoral vasculature as an approach to inhibit the proliferation of cancer cells, by using a novel synthetic molecule. We have developed a series of novel synthetic molecule 4-[2-(5-substituted-phenoxymethyl/ propyl)-[1,3,4]-oxadiazol-2-ylsulfanyl)-ethyl]-morpholine analogs 6a–l, which is a combination of oxadiazole and morpholine in a compact system. Among the synthesized series, the research team at MBL has identified a potent neoplastic and antiangiogenic drug – 6a, which had prolonged the survival of the tumor bearing animal by repressing the CD31 Microvessel density (MVD) and tumor recurrence. With this compound, MBL has identified and developed four potent anti-angiogenic and tumor suppressor drug with the others being BP-1B (Synthetic), BP-1T (Synthetic), Lupeol (Plant derived triterpenoid) etc.

This research article is published in the journal Bioorganic Chemistry (2015) by the publisher Elsevier. The research publication is an outcome of joint collaboration comprising MBL research team and Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore. The authors of this article include, Mohammed Al-Ghorbani, V. Vigneshwaran, V. Lakshmi Ranganatha, B.T. Prabhakar, Shaukath Ara Khanum (names in the order as published in the journal). The compound synthesis and characterization were carried out by research team at Mysore. The study involving screening, cell culture (in-vitro) and in-vivo animal experimentation were done at MBL, Shimoga.

Abstract of the publication (As published in the journal- Bioorganic Chemistry):

A series of oxadiazole derivatives possessing morpholine 6a–l were synthesized by nucleophilic substitution reaction of key intermediates [1,3,4]-oxadiazole-2-thiol derivatives 5a–l with 4-(2-chloroethyl) morpholine. Compounds 6a–l were evaluated for their in vitro and in vivo antitumor potential in Dalton’s Lymphoma Ascites (DLA) tumor cells. Among 6a–l series, compound 6a with concentration ~8.5 μM have shown extensive cytotoxicity in vitro and 85% reduction in tumor volume in vivo, attributing an excellent anti-proliferative capability towards the cancer cells. Compound 6a has extensively inhibited the Microvessel Density (MVD) or tumoral neovasculature which was evident from the CD31 immuno staining and peritoneal H&E staining. The major reason for the antiproliferative activity of compound 6a was due to the repression of tumor vasculature. 

PUBMED LINK: http://www.ncbi.nlm.nih.gov/pubmed/26005956