PMID- 18752963
OWN - NLM
STAT- MEDLINE
DCOM- 20081205
LR  - 20191210
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 16
IP  - 18
DP  - 2008 Sep 15
TI  - Synthesis and biological evaluation of indolyl bisphosphonates as anti-bone 
      resorptive and anti-leishmanial agents.
PG  - 8482-91
LID - 10.1016/j.bmc.2008.08.024 [doi]
AB  - A series of indole conjugated bisphosphonate derivatives have been synthesized 
      and evaluated for their in vitro anti-bone resorptive activity using bone marrow 
      osteoclast culture. Two bisphosphonates 23 and 24 significantly inhibited 
      osteoclastogenesis, 23 showed inhibition at 10 and 100 pM which was lower than 
      the concentration of standard drug alendronate, and 24 inhibited 
      osteoclastogenesis at 100 nM which was comparable to alendronate. Two other 
      compounds 13 and 14 also showed inhibition comparable to alendronate, but were 
      cytotoxic in the osteoblast cells. The two active bisphosphonates 23 and 24 
      induced significant osteoclast apoptosis at concentrations 100 nM for compound 24 
      and at 10 pM for compound 23 compared to alendronate. In vivo effect of active 
      bisphosphonates 23 and 24 resulted in osteoclastogenesis of bone marrow cells 
      (BMCs) to almost 40-50% (23 showing 8.4% decrease and 24 showing 9.0%) compared 
      to 16.5% of the ovariectomized group. Further, screening of anti-leishmanial 
      activity, four compounds 24-25 and 27-28 showed more than 80% inhibition against 
      both the promastigote and amastigote stages of the Leishmania parasite.
FAU - Singh, Uma Sharan
AU  - Singh US
AD  - Medicinal & Process Chemistry Division, Central Drug Research Institute, Lucknow 
      226001, India.
FAU - Shankar, Ravi
AU  - Shankar R
FAU - Kumar, Avinash
AU  - Kumar A
FAU - Trivedi, Ritu
AU  - Trivedi R
FAU - Chattopadhyay, Naibedya
AU  - Chattopadhyay N
FAU - Shakya, Nishi
AU  - Shakya N
FAU - Palne, Shraddha
AU  - Palne S
FAU - Gupta, Suman
AU  - Gupta S
FAU - Hajela, K
AU  - Hajela K
LA  - eng
PT  - Evaluation Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080812
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (Bone Density Conservation Agents)
RN  - 0 (Diphosphonates)
RN  - 0 (Indoles)
RN  - X1J18R4W8P (Alendronate)
SB  - IM
MH  - Alendronate/pharmacology
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Bone Density Conservation Agents/chemical synthesis/*pharmacology
MH  - Bone Resorption/metabolism/*pathology
MH  - Cell Proliferation/*drug effects
MH  - Cells, Cultured
MH  - Diphosphonates/chemical synthesis/*pharmacology
MH  - Indoles/chemical synthesis/*pharmacology
MH  - Leishmania/*drug effects/metabolism
MH  - Mice
MH  - Osteoclasts/metabolism/pathology
MH  - Structure-Activity Relationship
EDAT- 2008/08/30 09:00
MHDA- 2008/12/17 09:00
CRDT- 2008/08/30 09:00
PHST- 2008/06/03 00:00 [received]
PHST- 2008/08/06 00:00 [revised]
PHST- 2008/08/08 00:00 [accepted]
PHST- 2008/08/30 09:00 [pubmed]
PHST- 2008/12/17 09:00 [medline]
PHST- 2008/08/30 09:00 [entrez]
AID - S0968-0896(08)00752-9 [pii]
AID - 10.1016/j.bmc.2008.08.024 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2008 Sep 15;16(18):8482-91. doi: 10.1016/j.bmc.2008.08.024. Epub 
      2008 Aug 12.