Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)

Dysregulation of P70 ribosomal S6 kinase (P70S6K) has been observed in many cancers; therefore, the design of new molecules targeting p70S6K of paramount importance in cancer therapy. The current study employed a group-based quantitative structure-activity relationship (GQSAR) to develop global QS...

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Main Authors:	Abdullahi, Abubakar Danjuma, Mohammed Abdul Kader, Abdul Rahman, Abdul Samat, Nadia Hanis, Mohamed, Farahidah, Muhammad, Bala Yauri, Mohammed, Helaluddin Abul bashar, Aljarbou, Ahmed, Kasmuri, Abdul Razak
Format:	Article
Language:	English
Published:	Journal of Applied Pharmaceutical Science (http://www.japsonline.com) 2014
Subjects:	RS Pharmacy and materia medica
Online Access:	http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/1/novel_insight_into_new_qsar_Japs.pdf

id	iium-41555
recordtype	eprints
spelling	iium-415552017-09-21T12:23:41Z http://irep.iium.edu.my/41555/ Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR) Abdullahi, Abubakar Danjuma Mohammed Abdul Kader, Abdul Rahman Abdul Samat, Nadia Hanis Mohamed, Farahidah Muhammad, Bala Yauri Mohammed, Helaluddin Abul bashar Aljarbou, Ahmed Kasmuri, Abdul Razak RS Pharmacy and materia medica Dysregulation of P70 ribosomal S6 kinase (P70S6K) has been observed in many cancers; therefore, the design of new molecules targeting p70S6K of paramount importance in cancer therapy. The current study employed a group-based quantitative structure-activity relationship (GQSAR) to develop global QSAR models capable of predicting the bioactivity of P70S6K inhibitors. A wide variety of chemical structures and biological activities (half maximal inhibitory concentration) of P70S6K inhibitors were collected from the binding database website. Compounds were classified into various chemical groups and then fragmented into R1, R2, and R3 fragments based on certain pharmacophoric features required for ligand-target biointeractions. Different two-dimensional fragment-based descriptors were calculated for each fragment. The dataset was then divided into a training set (n=40) and a test set (n=10) using a sphere exclusion algorithm. Multiple linear regressions coupled with simulated annealing or stepwise regression resulted in model A (r2=0.92) and model B (r2=0.87), respectively. Leave-one-out validation showed that models A and B have internal predictive abilities of 72% and 61%, respectively. External validation indicated that both models are robust, with squared cross-correlation coefficients of the training set (pred-r2) of 0.87 and 0.89, respectively. The developed GQSAR models indicate that fragment R3 plays a key role in activity variation (65%) with sound contribution of five-membered rings (5 chain count), aromatic carbons (SaaaCE-index), and aromatic nitrogens (SaaNcount). In contrast, fragments R1 and R2 together contribute 35% of activity variation, suggesting that sulfur atoms (Sulfur count) and hydrophobic threemembered rings (chi3 chain) at R1 are preferable for inhibitory activity. Journal of Applied Pharmaceutical Science (http://www.japsonline.com) 2014-06 Article PeerReviewed application/pdf en http://irep.iium.edu.my/41555/1/novel_insight_into_new_qsar_Japs.pdf Abdullahi, Abubakar Danjuma and Mohammed Abdul Kader, Abdul Rahman and Abdul Samat, Nadia Hanis and Mohamed, Farahidah and Muhammad, Bala Yauri and Mohammed, Helaluddin Abul bashar and Aljarbou, Ahmed and Kasmuri, Abdul Razak (2014) Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR). Journal of Applied Pharmaceutical Science, 4 (6). pp. 16-24. ISSN 2231-3354 http://www.japsonline.com 10.7324/JAPS.2014.40603
repository_type	Digital Repository
institution_category	Local University
institution	International Islamic University Malaysia
building	IIUM Repository
collection	Online Access
language	English
topic	RS Pharmacy and materia medica
spellingShingle	RS Pharmacy and materia medica Abdullahi, Abubakar Danjuma Mohammed Abdul Kader, Abdul Rahman Abdul Samat, Nadia Hanis Mohamed, Farahidah Muhammad, Bala Yauri Mohammed, Helaluddin Abul bashar Aljarbou, Ahmed Kasmuri, Abdul Razak Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
description	Dysregulation of P70 ribosomal S6 kinase (P70S6K) has been observed in many cancers; therefore, the design of new molecules targeting p70S6K of paramount importance in cancer therapy. The current study employed a group-based quantitative structure-activity relationship (GQSAR) to develop global QSAR models capable of predicting the bioactivity of P70S6K inhibitors. A wide variety of chemical structures and biological activities (half maximal inhibitory concentration) of P70S6K inhibitors were collected from the binding database website. Compounds were classified into various chemical groups and then fragmented into R1, R2, and R3 fragments based on certain pharmacophoric features required for ligand-target biointeractions. Different two-dimensional fragment-based descriptors were calculated for each fragment. The dataset was then divided into a training set (n=40) and a test set (n=10) using a sphere exclusion algorithm. Multiple linear regressions coupled with simulated annealing or stepwise regression resulted in model A (r2=0.92) and model B (r2=0.87), respectively. Leave-one-out validation showed that models A and B have internal predictive abilities of 72% and 61%, respectively. External validation indicated that both models are robust, with squared cross-correlation coefficients of the training set (pred-r2) of 0.87 and 0.89, respectively. The developed GQSAR models indicate that fragment R3 plays a key role in activity variation (65%) with sound contribution of five-membered rings (5 chain count), aromatic carbons (SaaaCE-index), and aromatic nitrogens (SaaNcount). In contrast, fragments R1 and R2 together contribute 35% of activity variation, suggesting that sulfur atoms (Sulfur count) and hydrophobic threemembered rings (chi3 chain) at R1 are preferable for inhibitory activity.
format	Article
author	Abdullahi, Abubakar Danjuma Mohammed Abdul Kader, Abdul Rahman Abdul Samat, Nadia Hanis Mohamed, Farahidah Muhammad, Bala Yauri Mohammed, Helaluddin Abul bashar Aljarbou, Ahmed Kasmuri, Abdul Razak
author_facet	Abdullahi, Abubakar Danjuma Mohammed Abdul Kader, Abdul Rahman Abdul Samat, Nadia Hanis Mohamed, Farahidah Muhammad, Bala Yauri Mohammed, Helaluddin Abul bashar Aljarbou, Ahmed Kasmuri, Abdul Razak
author_sort	Abdullahi, Abubakar Danjuma
title	Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
title_short	Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
title_full	Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
title_fullStr	Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
title_full_unstemmed	Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)
title_sort	novel insight into the structural requirements of p70s6k inhibition using group-based quantitative structure activity relationship (gqsar) (gqsar)
publisher	Journal of Applied Pharmaceutical Science (http://www.japsonline.com)
publishDate	2014
url	http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/ http://irep.iium.edu.my/41555/1/novel_insight_into_new_qsar_Japs.pdf
first_indexed	2023-09-18T20:59:30Z
last_indexed	2023-09-18T20:59:30Z
_version_	1777410527844106240

Novel insight into the structural requirements of P70S6K inhibition using group-based quantitative structure activity relationship (GQSAR) (GQSAR)

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