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. |
| Mr. V. Vigneshwaran |
Abstract of the
publication (As published by 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.
