The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies

Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objecctive of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their im...

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Published in:Bioorganic Chemistry
Main Author: Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
Format: Article
Language:English
Published: Academic Press Inc. 2016
Online Access:https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948428551&doi=10.1016%2fj.bioorg.2015.11.004&partnerID=40&md5=7a038355f5ed15e353779b28c15c7d49
id 2-s2.0-84948428551
spelling 2-s2.0-84948428551
Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
2016
Bioorganic Chemistry
64

10.1016/j.bioorg.2015.11.004
https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948428551&doi=10.1016%2fj.bioorg.2015.11.004&partnerID=40&md5=7a038355f5ed15e353779b28c15c7d49
Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objecctive of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P < 0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases. © 2015 Published by Elsevier Inc.
Academic Press Inc.
452068
English
Article

author Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
spellingShingle Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
author_facet Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
author_sort Khan K.M.; Mesaik M.A.; Abdalla O.M.; Rahim F.; Soomro S.; Halim S.A.; Mustafa G.; Ambreen N.; Khalid A.S.; Taha M.; Perveen S.; Alam M.T.; Hameed A.; Ul-Haq Z.; Ullah H.; Rehman Z.U.; Siddiqui R.A.; Voelter W.
title The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
title_short The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
title_full The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
title_fullStr The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
title_full_unstemmed The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
title_sort The immunomodulation potential of the synthetic derivatives of benzothiazoles: Implications in immune system disorders through in vitro and in silico studies
publishDate 2016
container_title Bioorganic Chemistry
container_volume 64
container_issue
doi_str_mv 10.1016/j.bioorg.2015.11.004
url https://www.scopus.com/inward/record.uri?eid=2-s2.0-84948428551&doi=10.1016%2fj.bioorg.2015.11.004&partnerID=40&md5=7a038355f5ed15e353779b28c15c7d49
description Benzothiazole and its natural or synthetic derivatives have been used as precursors for several pharmacological agents for neuroprotective, anti-bacterial, and anti-allergic activities. The objecctive of the present study was to evaluate effects of benzothiazole analogs (compounds 1-26) for their immunomodulatory activities. Eight compounds (2, 4, 5, 8-10, 12, and 18) showed potent inhibitory activity on PHA-activated peripheral blood mononuclear cells (PBMCs) with IC50 ranging from 3.7 to 11.9 μM compared to that of the standard drug, prednisolone <1.5 μM. Some compounds (2, 4, 8, and 18) were also found to have potent inhibitory activities on the production of IL-2 on PHA/PMA-stimulated PBMCs with IC50 values ranging between <4.0 and 12.8 μM. The binding interaction of these compounds was performed through silico molecular docking. Compounds 2, 8, 9, and 10 significantly suppressed oxidative burst ROS production in phagocytes with IC50 values between <4.0 and 15.2 μM. The lipopolysaccharide (LPS)-induced nitrites in murine macrophages cell line J774 were found to be inhibited by compounds 4, 8, 9, and 18 at a concentration of 25 μg/mL by 56%, 91%, 58%, and 78%, respectively. Furthermore, compounds 5, 8, 12, and 18 showed significant (P < 0.05) suppressive activity on Th-2 cytokine, interleukin 4 (IL-4) with an IC50 range of <4.0 to 40.3 μM. Interestingly compound 4 has shown a selective inhibitory activity on IL-2 and T cell proliferation (naïve T cell proliferation stage) rather than on IL-4 cytokine, while compound 12 displayed an interference with T-cell proliferation and IL-4 generation. Moreover compound 8 and 18 exert non-selective inhibition on both IL-2 and IL-4 cytokines, indicating a better interference with stage leading to humoral immune response and hence possible application in autoimmune diseases. © 2015 Published by Elsevier Inc.
publisher Academic Press Inc.
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