creators_name: Upadhyay, Rahul
creators_name: Kumar, Rahul
creators_name: Jangra, Manoj
creators_name: Rana, Rohit
creators_name: Nayal, Onkar S
creators_name: Nandanwar, Hemraj
creators_name: Maurya, Sushil K
type: article
datestamp: 2020-07-30 11:41:23
lastmod: 2020-10-20 04:19:22
metadata_visibility: show
title: Synthesis of Bioactive Complex Small Molecule-Ciprofloxacin Conjugates and Evaluation of Their Antibacterial Activity
ispublished: pub
subjects: QR
keywords: 1,2,3-triazole; antibacterial agents; ciprofloxacin; click chemistry.
note: Copyright of this article belongs to ACS.
abstract: Conjugates between pharmaceuticals and small molecules enable access to a vast chemical space required for the discovery of new lead molecules with modified therapeutic potential. However, the dearth of specific chemical reactions that are capable of functionalizing drugs and bioactive natural products presents a formidable challenge for preparing their conjugates. Here, we report a support-free CuI-nanoparticle-catalyzed strategy for conjugating electron-deficient and electron-rich terminal alkynes with a ciprofloxacin methyl ester. Our conjugation technique exploits the late-stage functionalization of bioactive natural products such as tocopherol, vasicinone, amino acids, and pharmaceuticals such as aspirin and paracetamol to provide conjugates in excellent yields under mild and green conditions. This protocol also enabled the synthesis of (hetero)arene-ciprofloxacin 1,4-disubstituted 1,2,3-triazoles in good yields and high regioselectivities. These synthesized ciprofloxacin conjugates were evaluated in vitro for their antibacterial activity against a panel of relevant bacteria. A significant number of conjugates showed comparable activity against Gram-positive and Gram-negative bacteria. Moreover, some conjugates exhibited less toxicity than ciprofloxacin against two mammalian cell lines, suggesting the utility for the future investigation of these compounds for in vivo efficacy and pharmacokinetic studies.
date: 2020-07-21
date_type: published
publication: ACS Combinatorial Science
volume: 22
number: 9
publisher: American Chemical Society
pagerange: 440-445
refereed: TRUE
official_url: https://pubs.acs.org/doi/10.1021/acscombsci.0c00060
citation:   Upadhyay, Rahul and Kumar, Rahul and Jangra, Manoj and Rana, Rohit and Nayal, Onkar S and Nandanwar, Hemraj and Maurya, Sushil K  (2020) Synthesis of Bioactive Complex Small Molecule-Ciprofloxacin Conjugates and Evaluation of Their Antibacterial Activity.  ACS Combinatorial Science, 22 (9).  pp. 440-445.