Discovery of a New Class of Natural Product-Inspired Quinazolinone Hybrid as Potent Antileishmanial agents
IR@CDRI: CSIR-Central Drug Research Institute, Lucknow
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| Creator |
Sharma, Moni
Chauhan, Kuldeep Shivahare, Rahul Vishwakarma, Preeti Suthar, M K Sharma, Abhisheak Gupta, Suman Saxena, J K Lal, Jawahar Chandra, Preeti Kumar, Brijesh Chauhan, P M S |
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| Date |
2013-07-05T11:27:17Z
2013-07-05T11:27:17Z 2013 |
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| Identifier |
Journal of Medicinal. Chemistry, 2013, 56, 4374−4392
http://hdl.handle.net/123456789/1083 |
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| Description |
The high potential of quinazolinone containing natural products and their derivatives in medicinal chemistry led us to discover four novel series of 53 compounds of quinazolinone based on the concept of molecular hybridization. Most of the synthesized analogues exhibited potent leishmanicidal activity against intracellular amastigotes (IC50 from 0.65 ± 0.2 to 7.76 ± 2.1 μM) as compared to miltefosine (IC50 = 8.4 ± 2.1 μM) and non toxic towards J-774A.1 cell line and vero cells. Moreover, activation of Th1 type, and suppression of Th2 type immune responses and induction in nitric oxide generation proved that 8a and 8g induce murine macrophages to prevent survival of parasite. Compounds 8a and 8g exhibited significant in vivo inhibition of parasite 73.15 ± 12.69% and 80.93 ± 10.50% against L. donovani / hamster model. Our results indicate that compounds 8a, 8g, and 9f represent a new structural lead for this serious and neglected disease.
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2798225 bytes
application/pdf |
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| Language |
en
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| Relation |
CDRI Communication No. 8453
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| Subject |
Quinazolinone
Potent Antileishmanial |
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| Title |
Discovery of a New Class of Natural Product-Inspired Quinazolinone Hybrid as Potent Antileishmanial agents
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| Type |
Article
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