Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids

Kunal Nepali, Sahil Sharma, Manmohan Sharma, P. M.S. Bedi, K. L. Dhar

研究成果: 雜誌貢獻回顧型文獻

192 引文 (Scopus)

摘要

A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part.The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids. 2014 Elsevier Masson SAS. All rights reserved.
原文英語
頁(從 - 到)422-487
頁數66
期刊European Journal of Medicinal Chemistry
77
DOIs
出版狀態已發佈 - 四月 22 2014
對外發佈Yes

指紋

Structure-Activity Relationship
Tubulin
Pharmaceutical Preparations
Isatin
Chalcones
Vinca Alkaloids
Coumarins
Molecules
Colchicine
Paclitaxel
Antineoplastic Agents
Drug Design
Steroids
Streptomyces
Protein Transport
Anti-Bacterial Agents
Microtubules
DNA
Research Personnel
Proteins

ASJC Scopus subject areas

  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

引用此文

Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids. / Nepali, Kunal; Sharma, Sahil; Sharma, Manmohan; Bedi, P. M.S.; Dhar, K. L.

於: European Journal of Medicinal Chemistry, 卷 77, 22.04.2014, p. 422-487.

研究成果: 雜誌貢獻回顧型文獻

@article{8c6cd4b473b048769152167c35eff85f,
title = "Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids",
abstract = "A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part.The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids. 2014 Elsevier Masson SAS. All rights reserved.",
keywords = "Cancer, Colchicine, Cytotoxic, Fusion, Molecular hybridization, Tubulin",
author = "Kunal Nepali and Sahil Sharma and Manmohan Sharma and Bedi, {P. M.S.} and Dhar, {K. L.}",
year = "2014",
month = "4",
day = "22",
doi = "10.1016/j.ejmech.2014.03.018",
language = "English",
volume = "77",
pages = "422--487",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",

}

TY - JOUR

T1 - Rational approaches, design strategies, structure activity relationship and mechanistic insights for anticancer hybrids

AU - Nepali, Kunal

AU - Sharma, Sahil

AU - Sharma, Manmohan

AU - Bedi, P. M.S.

AU - Dhar, K. L.

PY - 2014/4/22

Y1 - 2014/4/22

N2 - A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part.The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids. 2014 Elsevier Masson SAS. All rights reserved.

AB - A Hybrid drug which comprises the incorporation of two drug pharmacophores in one single molecule are basically designed to interact with multiple targets or to amplify its effect through action on another bio target as one single molecule or to counterbalance the known side effects associated with the other hybrid part.The present review article offers a detailed account of the design strategies employed for the synthesis of anticancer agents via molecular hybridization techniques. Over the years, the researchers have employed this technique to discover some promising chemical architectures displaying significant anticancer profiles. Molecular hybridization as a tool has been particularly utilized for targeting tubulin protein as exemplified through the number of research papers. The microtubule inhibitors such as taxol, colchicine, chalcones, combretasatin, phenstatins and vinca alkaloids have been utilized as one of the functionality of the hybrids and promising results have been obtained in most of the cases with some of the tubulin based hybrids exhibiting anticancer activity at nanomolar level. Linkage with steroids as biological carrier vector for anticancer drugs and the inclusion of pyrrolo [2,1-c] [1,4]benzodiazepines (PBDs), a family of DNA interactive antitumor antibiotics derived from Streptomyces species in hybrid structure based drug design has also emerged as a potential strategy. Various heteroaryl based hybrids in particular isatin and coumarins have also been designed and reported to posses' remarkable inhibitory potential. Apart from presenting the design strategies, the article also highlights the structure activity relationship along with mechanistic insights revealed during the biological evaluation of the hybrids. 2014 Elsevier Masson SAS. All rights reserved.

KW - Cancer

KW - Colchicine

KW - Cytotoxic

KW - Fusion

KW - Molecular hybridization

KW - Tubulin

UR - http://www.scopus.com/inward/record.url?scp=84897386255&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84897386255&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2014.03.018

DO - 10.1016/j.ejmech.2014.03.018

M3 - Review article

C2 - 24685980

AN - SCOPUS:84897386255

VL - 77

SP - 422

EP - 487

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

ER -