PMID- 26487913
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20151021
LR  - 20201001
IS  - 1948-5875 (Print)
IS  - 1948-5875 (Electronic)
IS  - 1948-5875 (Linking)
VI  - 6
IP  - 10
DP  - 2015 Oct 8
TI  - Design, Synthesis, and Biological Evaluation of 1,2-Dihydroisoquinolines as HIV-1 
      Integrase Inhibitors.
PG  - 1065-70
LID - 10.1021/acsmedchemlett.5b00230 [doi]
AB  - 6-Endo-dig-cyclization is an efficient method for the synthesis of 
      1,2-dihydroisoquinolines. We have synthesized few 1,2-dihydroisoquinolines having 
      different functionality at the C-1, C-3, C-7, and N-2 positions for evaluation 
      against HIV-1 integrase (HIV1-IN) inhibitory activity. A direct nitro-Mannich 
      condensation of o-alkynylaldimines and dual activation of o-alkynyl aldehydes by 
      inexpensive cobalt chloride yielded desired compounds. Out of 24 compounds, 4m 
      and 6c came out as potent integrase inhibitors in in vitro strand transfer (ST) 
      assay, with IC50 value of 0.7 and 0.8 muM, respectively. Molecular docking of 
      these compounds in integrase revealed strong interaction between metal and 
      ligands, which stabilizes the enzyme-inhibitor complex. The ten most active 
      compounds were subjected to antiviral assay. Out of those, 6c reduced the level 
      of p24 viral antigen by 91%, which is comparable to RAL in antiviral assay. 
      Interestingly, these compounds showed similar ST inhibitory activity in G140S 
      mutant, suggesting they can act against resistant strains.
FAU - Tandon, Vibha
AU  - Tandon V
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India ; Special 
      Centre for Molecular Medicine, Jawaharlal Nehru University , New Delhi 110067, 
      India.
FAU - Urvashi
AU  - Urvashi
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Yadav, Pooja
AU  - Yadav P
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Sur, Souvik
AU  - Sur S
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Abbat, Sheenu
AU  - Abbat S
AD  - National Institute of Pharmaceutical Education and Research , S. A. S Nagar, 
      Mohali, Punjab 160062, India.
FAU - Tiwari, Vinod
AU  - Tiwari V
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Hewer, Raymond
AU  - Hewer R
AD  - Biomedical Advanced Material Division, Mintek , Private Bag X3015, Randburg 2125, 
      Johannesburg, South Africa.
FAU - Papathanasopoulos, Maria A
AU  - Papathanasopoulos MA
AD  - Department of Molecular Medicine and Haematology, University of the Witwatersrand 
      Medical School , Parktown 2193, Johannesburg, South Africa.
FAU - Raja, Rameez
AU  - Raja R
AD  - Laboratory of Virology, National Institute of Immunology , New Delhi 110067, 
      India.
FAU - Banerjea, Akhil C
AU  - Banerjea AC
AD  - Laboratory of Virology, National Institute of Immunology , New Delhi 110067, 
      India.
FAU - Verma, Akhilesh K
AU  - Verma AK
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Kukreti, Shrikant
AU  - Kukreti S
AD  - Department of Chemistry, University of Delhi , Delhi 110007, India.
FAU - Bharatam, Prasad V
AU  - Bharatam PV
AD  - National Institute of Pharmaceutical Education and Research , S. A. S Nagar, 
      Mohali, Punjab 160062, India.
LA  - eng
PT  - Journal Article
DEP - 20150810
PL  - United States
TA  - ACS Med Chem Lett
JT  - ACS medicinal chemistry letters
JID - 101521073
PMC - PMC4601057
OTO - NOTNLM
OT  - Multicomponent reaction
OT  - integrase
OT  - integrase inhibitors
OT  - molecular docking
COIS- The authors declare no competing financial interest.
EDAT- 2015/10/22 06:00
MHDA- 2015/10/22 06:01
PMCR- 2016/10/08
CRDT- 2015/10/22 06:00
PHST- 2015/06/09 00:00 [received]
PHST- 2015/08/09 00:00 [accepted]
PHST- 2015/10/22 06:00 [entrez]
PHST- 2015/10/22 06:00 [pubmed]
PHST- 2015/10/22 06:01 [medline]
PHST- 2016/10/08 00:00 [pmc-release]
AID - 10.1021/acsmedchemlett.5b00230 [doi]
PST - epublish
SO  - ACS Med Chem Lett. 2015 Aug 10;6(10):1065-70. doi: 
      10.1021/acsmedchemlett.5b00230. eCollection 2015 Oct 8.