TY - JOUR
T1 - Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols
AU - Ahmed, Nafees
AU - Brahmbhatt, Keyur G.
AU - Sabde, Sudeep
AU - Mitra, Debashis
AU - Singh, Inder Pal
AU - Bhutani, Kamlesh K.
N1 - Funding Information:
Authors thank the Department of Biotechnology, Ministry of Science and Technology, Government of India for the financial support to this project (Grant No. BT/PR7020/Med/14/930/2005 Dt. 23/05/2006 ).
Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2010/4/15
Y1 - 2010/4/15
N2 - Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1NL4.3 virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC50 value of 2.99 and 3.80 μM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC50 value of 2.35 μM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC50 values which indicate that they have better therapeutic indices.
AB - Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1NL4.3 virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC50 value of 2.99 and 3.80 μM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC50 value of 2.35 μM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC50 values which indicate that they have better therapeutic indices.
KW - Alkylation
KW - Anti-HIV activity
KW - CEM-GFP cells
KW - Quinoline 2,4-diol
UR - http://www.scopus.com/inward/record.url?scp=77950629689&partnerID=8YFLogxK
U2 - 10.1016/j.bmc.2010.03.015
DO - 10.1016/j.bmc.2010.03.015
M3 - Article
C2 - 20350812
AN - SCOPUS:77950629689
SN - 0968-0896
VL - 18
SP - 2872
EP - 2879
JO - Bioorganic & Medicinal Chemistry
JF - Bioorganic & Medicinal Chemistry
IS - 8
ER -
