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A Versatile Pre and Post Ugi Modification for the Synthesis of Natural Product Inspired Fused Peptide‐Carboline Scaffolds as Potential Anti‐Leishmanial Agents
Author(s) -
Khan Irfan,
Singh Jaybir,
Kumar Vivek,
Verma Ved Prakash,
Shukla Monika,
Dhasmana Anupam,
Naruka Puspendera Singh,
Goswami Ajay Kumar,
Ameta Keshav Lalit,
Khan Shahnawaz
Publication year - 2019
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.201902441
Subject(s) - miltefosine , sodium stibogluconate , natural product , peptide , cytotoxicity , amastigote , leishmania donovani , chemistry , in vitro , ic50 , stereochemistry , combinatorial chemistry , leishmaniasis , pharmacology , leishmania , biochemistry , biology , cutaneous leishmaniasis , visceral leishmaniasis , immunology , computer science , parasite hosting , world wide web
A series of novel β ‐ carboline‐peptide ( 5 a‐5 f )/ tetrahydro‐β‐carbolines‐peptide ( 10 a‐10 f ) has been synthesized via natural product inspired molecular hybridization approach. All the hybrids were examined for their anti‐leishmanial potential. Most of the screened derivatives exhibited significant in vitro anti‐leishmanial activity against promastigote and intracellular amastigotes (IC 50 ranging from 2.43 to 7.61 μ M) than the control, miltefosine (IC 50 = 8.2 μ M) , with less cytotoxicity in comparison to the standard drugs (sodium stibogluconate, and miltefosine). Compound 5 a was also able to inhibit Leishmania donovani TR (LdTR). A molecular modeling study based on docking and subsequent binding free energy evaluation was carry out in the active site of LdTR to understand their possible binding site. Our results show that prototype 1 ( 5 a‐5 f ) & 2 ( 10 a‐10 f ) represent a new structural lead for anti‐leishmanial Chemotherapy.