Abstract

A-ring modifications of betulinic acid isolated from Diospyros peregrina was carried out and the chemically modified derivatives were characterized by spectroscopic methods. Chemically modified betulinic acid analogues were subjected to molecular docking studies on topoisomerase-1 and were evaluated for in vitro and in vivo anticancer activity. In vitro anticancer studies revealed that among semisynthetic derivatives of betulinic acid the 2- benzylidene derivatives BE-6 and BE-7 as the most active compounds against HeLa and MDA-MB-435 cell lines. Compounds BE-6 and BE-7 exhibited apoptosis-mediated cell death and caused cell cycle arrest at the G0/G1 phase of HeLa cells. The in vivo Ehrlich ascites carcinoma model further confirms the antitumor efficacy BE-6 and BE-7. Molecular docking studies reveal that introduction of benzylidene group in the second position of betulinic acid has improved the binding affinity to topoisomerase-1. Further, the anticancer property of betulinic acid derivatives was in agreement with molecular docking results.

Original languageEnglish
Pages (from-to)1582-1590
Number of pages9
JournalLatin American Journal of Pharmacy
Volume38
Issue number8
Publication statusPublished - 01-01-2019

Fingerprint

Diospyros
Cell Cycle Resting Phase
G1 Phase
Cell Cycle Checkpoints
HeLa Cells
Ascites
Cell Death
In Vitro Techniques
betulinic acid
Apoptosis
Carcinoma
Cell Line
hexaoxyethylenated trisiloxane

All Science Journal Classification (ASJC) codes

  • Pharmaceutical Science
  • Drug Discovery

Cite this

Joseph, Alex ; Srinivasan, Keloth K. ; Kutty, Nampurath G. ; Moorkoth, Sudheer ; Alex, Angel T. ; Maliyakkal, Naseer. / In vitro and in vivo anticancer activity of semisynthetic derivatives of betulinic acid. In: Latin American Journal of Pharmacy. 2019 ; Vol. 38, No. 8. pp. 1582-1590.
@article{d4c714e29eb94725b7914a504107e563,
title = "In vitro and in vivo anticancer activity of semisynthetic derivatives of betulinic acid",
abstract = "A-ring modifications of betulinic acid isolated from Diospyros peregrina was carried out and the chemically modified derivatives were characterized by spectroscopic methods. Chemically modified betulinic acid analogues were subjected to molecular docking studies on topoisomerase-1 and were evaluated for in vitro and in vivo anticancer activity. In vitro anticancer studies revealed that among semisynthetic derivatives of betulinic acid the 2- benzylidene derivatives BE-6 and BE-7 as the most active compounds against HeLa and MDA-MB-435 cell lines. Compounds BE-6 and BE-7 exhibited apoptosis-mediated cell death and caused cell cycle arrest at the G0/G1 phase of HeLa cells. The in vivo Ehrlich ascites carcinoma model further confirms the antitumor efficacy BE-6 and BE-7. Molecular docking studies reveal that introduction of benzylidene group in the second position of betulinic acid has improved the binding affinity to topoisomerase-1. Further, the anticancer property of betulinic acid derivatives was in agreement with molecular docking results.",
author = "Alex Joseph and Srinivasan, {Keloth K.} and Kutty, {Nampurath G.} and Sudheer Moorkoth and Alex, {Angel T.} and Naseer Maliyakkal",
year = "2019",
month = "1",
day = "1",
language = "English",
volume = "38",
pages = "1582--1590",
journal = "Latin American Journal of Pharmacy",
issn = "0326-2383",
publisher = "Colegio de Farmaceuticos de la Provincia de Buenos Aires",
number = "8",

}

In vitro and in vivo anticancer activity of semisynthetic derivatives of betulinic acid. / Joseph, Alex; Srinivasan, Keloth K.; Kutty, Nampurath G.; Moorkoth, Sudheer; Alex, Angel T.; Maliyakkal, Naseer.

In: Latin American Journal of Pharmacy, Vol. 38, No. 8, 01.01.2019, p. 1582-1590.

Research output: Contribution to journalArticle

TY - JOUR

T1 - In vitro and in vivo anticancer activity of semisynthetic derivatives of betulinic acid

AU - Joseph, Alex

AU - Srinivasan, Keloth K.

AU - Kutty, Nampurath G.

AU - Moorkoth, Sudheer

AU - Alex, Angel T.

AU - Maliyakkal, Naseer

PY - 2019/1/1

Y1 - 2019/1/1

N2 - A-ring modifications of betulinic acid isolated from Diospyros peregrina was carried out and the chemically modified derivatives were characterized by spectroscopic methods. Chemically modified betulinic acid analogues were subjected to molecular docking studies on topoisomerase-1 and were evaluated for in vitro and in vivo anticancer activity. In vitro anticancer studies revealed that among semisynthetic derivatives of betulinic acid the 2- benzylidene derivatives BE-6 and BE-7 as the most active compounds against HeLa and MDA-MB-435 cell lines. Compounds BE-6 and BE-7 exhibited apoptosis-mediated cell death and caused cell cycle arrest at the G0/G1 phase of HeLa cells. The in vivo Ehrlich ascites carcinoma model further confirms the antitumor efficacy BE-6 and BE-7. Molecular docking studies reveal that introduction of benzylidene group in the second position of betulinic acid has improved the binding affinity to topoisomerase-1. Further, the anticancer property of betulinic acid derivatives was in agreement with molecular docking results.

AB - A-ring modifications of betulinic acid isolated from Diospyros peregrina was carried out and the chemically modified derivatives were characterized by spectroscopic methods. Chemically modified betulinic acid analogues were subjected to molecular docking studies on topoisomerase-1 and were evaluated for in vitro and in vivo anticancer activity. In vitro anticancer studies revealed that among semisynthetic derivatives of betulinic acid the 2- benzylidene derivatives BE-6 and BE-7 as the most active compounds against HeLa and MDA-MB-435 cell lines. Compounds BE-6 and BE-7 exhibited apoptosis-mediated cell death and caused cell cycle arrest at the G0/G1 phase of HeLa cells. The in vivo Ehrlich ascites carcinoma model further confirms the antitumor efficacy BE-6 and BE-7. Molecular docking studies reveal that introduction of benzylidene group in the second position of betulinic acid has improved the binding affinity to topoisomerase-1. Further, the anticancer property of betulinic acid derivatives was in agreement with molecular docking results.

UR - http://www.scopus.com/inward/record.url?scp=85073323496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85073323496&partnerID=8YFLogxK

M3 - Article

AN - SCOPUS:85073323496

VL - 38

SP - 1582

EP - 1590

JO - Latin American Journal of Pharmacy

JF - Latin American Journal of Pharmacy

SN - 0326-2383

IS - 8

ER -