alexa Receptor Chemoprint Derived Pharmacophore Model for Development of CAIX Inhibitors | OMICS International | Abstract
ISSN: 2157-2518

Journal of Carcinogenesis & Mutagenesis
Open Access

Like us on:

OMICS International organises 3000+ Global Conferenceseries Events every year across USA, Europe & Asia with support from 1000 more scientific Societies and Publishes 700+ Open Access Journals which contains over 50000 eminent personalities, reputed scientists as editorial board members.

Open Access Journals gaining more Readers and Citations
700 Journals and 15,000,000 Readers Each Journal is getting 25,000+ Readers

This Readership is 10 times more when compared to other Subscription Journals (Source: Google Analytics)

Research Article

Receptor Chemoprint Derived Pharmacophore Model for Development of CAIX Inhibitors

Prakash Amresh, Kundan Kumar, Asimul Islam, Md. Imtaiyaz Hassan* and Faizan Ahmad

Centre for Interdisciplinary Research in Basic Sciences, Jamia Millia Islamia, Jamia Nagar, New Delhi 110025, India

*Corresponding Author:
Imtaiyaz Hassan Md, Ph.D
Centre for Interdisciplinary Research in Basic Sciences
Jamia Millia Islamia, Jamia Nagar
New Delhi 110025, India
Tel: +91-11-2698-3409
E-mail: [email protected]

Received date: October 03, 2013; Accepted date: November 17, 2013; Published date: November 23, 2013

Citation: Amresh P, Kumar K, Islam A, Hassan I, Ahmad F (2013) Receptor Chemoprint Derived Pharmacophore Model for Development of CAIX Inhibitors. J Carcinog Mutagen S8:003. doi: 10.4172/2157-2518.S8-003

Copyright: © 2013 Amresh P, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Carbonic anhydrase IX (CAIX) is an attractive target for anticancer therapy because it is selectively overexpressed in tumor cells. Various CAs’ inhibitors (sulfonamides/sulfaumates and coumarins) are reported as promising anti-cancer agents, showed appreciable affinity and selectivity. Novel chemical scaffolds with improved pharmacological properties are essential for the development of safe and potent CAIX inhibitors. Materials and methods: Crystal structure of CAIX with its inhibitors revealed critical residues of CAIX that interacts to inhibitor(s). These information was used to design a receptor-chemoprint based pharmacophore model. In silico pharmacokinetic assays were carried for novel hits with both ADMET and TOPKAT tools of Discovery Studio 3.5. Results: Pharmacophore model consists of one hydrogen bond donor, three hydrogen bond acceptors, and two hydrophobic moieties which are defined as essential feature for CAIX inhibitors. Virtual screening of ZINC chemical databases leads to identification of 1242 hits, having pharmacophore fit score ≥ 0.95. These hits were subsequently subjected to molecular docking analysis but they are limited to 321 only. Conclusion: Based on consensus scoring values, critical interactions with active site residues, and predicted activity values, five compounds (ZINC03363328, ZINC08828920, ZINC12941947, ZINC03622539 and ZINC16650541) are proposed as possible lead for CAIX inhibitor. Present study suggests that a conceptual adjustment of these hits may lead to rational design of novel and potent CAIX inhibitor.

Keywords

Peer Reviewed Journals
 
Make the best use of Scientific Research and information from our 700 + peer reviewed, Open Access Journals
International Conferences 2018-19
 
Meet Inspiring Speakers and Experts at our 3000+ Global Annual Meetings

Contact Us

Agri & Aquaculture Journals

Dr. Krish

[email protected]

+1-702-714-7001Extn: 9040

Biochemistry Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Business & Management Journals

Ronald

[email protected]

1-702-714-7001Extn: 9042

Chemistry Journals

Gabriel Shaw

[email protected]

1-702-714-7001Extn: 9040

Clinical Journals

Datta A

[email protected]

1-702-714-7001Extn: 9037

Engineering Journals

James Franklin

[email protected]

1-702-714-7001Extn: 9042

Food & Nutrition Journals

Katie Wilson

[email protected]

1-702-714-7001Extn: 9042

General Science

Andrea Jason

[email protected]

1-702-714-7001Extn: 9043

Genetics & Molecular Biology Journals

Anna Melissa

[email protected]

1-702-714-7001Extn: 9006

Immunology & Microbiology Journals

David Gorantl

[email protected]

1-702-714-7001Extn: 9014

Materials Science Journals

Rachle Green

[email protected]

1-702-714-7001Extn: 9039

Nursing & Health Care Journals

Stephanie Skinner

[email protected]

1-702-714-7001Extn: 9039

Medical Journals

Nimmi Anna

[email protected]

1-702-714-7001Extn: 9038

Neuroscience & Psychology Journals

Nathan T

[email protected]

1-702-714-7001Extn: 9041

Pharmaceutical Sciences Journals

Ann Jose

[email protected]

1-702-714-7001Extn: 9007

Social & Political Science Journals

Steve Harry

[email protected]

1-702-714-7001Extn: 9042

 
© 2008- 2018 OMICS International - Open Access Publisher. Best viewed in Mozilla Firefox | Google Chrome | Above IE 7.0 version
Leave Your Message 24x7