Research Article | Volume: 8, Issue: 8, August, 2018

Novel synthetic analogues of Fluoxetine as potent and selective anti-TB agents

M. Murali Krishna Kumar K. Madhavi T. Mohan K. Purna Nagasree G. P. V. Sangeeta   

Open Access   

Published:  Aug 31, 2018

DOI: 10.7324/JAPS.2018.8815
Abstract

We have recently identified potent anti-TB activity in several CNS drugs. Most prominently, the phenothiazine antipsychotics (Thioridazine-MIC 3.125 μg/mL) and anti-depressant drugs (sertraline-MIC 1.6 μg/mL) have shown anti-TB activity against Mycobacterium tuberculosis H37Rv. In continuation, we have synthesized a series of 1-(3-aryloxy-3-phenylpropyl) amine analogues of fluoxetine to optimize its anti-TB activity. Identities of the synthesized compounds were confirmed by FTIR, 1H NMR and mass spectral analysis. They were tested for in vitro antitubercular activity by MABA Assay. To determine selective TB activity, they were also tested for antimicrobial activity. Among the synthesized compounds, 1-(3-(4-fluorophenoxy)-3-phenylpropyl) piperidine (AM3e) has shown highest anti-TB activity (MIC 1.6 μg/mL) against MtbH37Rv and is free from antibacterial/antifungal activity (MIC >100 μg/mL).


Keyword:     Acetophenone mannichbases fluoxetineantitubercular activity drugrepurposing.


Citation:

Kumar MMK, Madhavi K, Mohan T, Nagasree KP, Sangeeta GPV. Novel synthetic analogues of Fluoxetine as potent and selective anti-TB agents . J App Pharm Sci, 2018; 8(08): 107-115.

Copyright: © The Author(s). This is an open-access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HTML Full Text

Reference

Ali S, Hosseein F, Farshid M, Naimi Jamal MR. Microwave Assisted Mannich Reaction of Terminal Alkynes on Alumina. Monatshefte fur Chemie, 2002; 133:199-204. https://doi.org/10.1007/s706-002-8251-8

Andersen J, Kristensen AS, Bang-Andersen B, Strømgaard K. Recent advances in the understanding of the interaction of antidepressant drugs with serotonin and norepinephrine transporters. ChemComm, 2009; 25:3677-3692. https://doi.org/10.1039/b903035m

Juan Carlos P, Anandi M. Drug Resistance Mechanisms in Mycobacterium tuberculosis. Antibiotics, 2014; 85:317-340.

Daouk KD, Dagher MS, Sattout J. Antifungal Activity of the Essential Oil of Origanumsyriacum. L. J Food Prot, 1995; 58:1147-1149. https://doi.org/10.4315/0362-028X-58.10.1147

Franzblau SG, Witzig RS, McLaughlin JC, Torres P, Madico G, Hernandez A, Degnan MT, Cook MB, Quenzer VK, Ferguson RM and Gilman RH. Rapid, low-technology MIC determination with clinical Mycobacterium tuberculosis isolates by using the microplate Alamar Blue assay. J Clin.Microbiol, 1998; 36:362-366.

Hanel H, Raether W. A More Sophisticated Method of Determining the Fungicidal Effect of Water-Insoluble Preparations with a Cell Harvester, Using Miconazole as an Example. Mycoses, 1988; 31:148- 154. https://doi.org/10.1111/j.1439-0507.1988.tb03718.x

Hari Babu Bolikala, Balaji Neduri V, Gottumukkala V Subbaraju, Purna Nagasree Kurre, Murali Krishna Kumar Muthyala. Synthesis, Screening and Docking Analysis of Hispolon analogs as Potential Antitubercular Agents. Bioorg. Med. Chem. Lett, 2017; 27:11-15. https://doi.org/10.1016/j.bmcl.2016.11.047

Ianni A, Waldvogel SR. Reliable and Versatile Synthesis of 2-Aryl-Substituted Cinnamic Acid Esters. Synthesis, 2006; 13:2103-2112.

Kristiansen JE, Hendricks O, Delvin T, Butterworth TS, Aagaard L, Christensen JB, Flores VC, Keyzer H. Reversal of resistance in microorganisms by help of non-antibiotics. J Antimicrob Chemother, 2007; 59:1271-1279. https://doi.org/10.1093/jac/dkm071

Andreas M Larsen B, Plenge P, Andersen J, Eildal JNN, Kristensen AS, Bogeso KP, Gether U, Stromgaard K, Bang-Andersen B, Loland CJ. Structure-activity relationship studies of citalopram derivatives: examining substituents conferring selectivity for the allosteric site in the 5‐HT transporter. British J Pharmacol, 2016; 173:925-936. https://doi.org/10.1111/bph.13411

Larsen MA, Plenge P, Andersen J, Eildal JN, Kristensen AS, Bogeso KP, Gether U, Stromgaard K, Bang-Andersen B, Loland CJ, British J Pharmacol, 2016; 173:925-936. https://doi.org/10.1111/bph.13411

Lass-Florl C, Dierich MP, Fuchs D, Semenitz E, Jenewein I, Ledochowski M. Antifungal properties of selective serotonin reuptake inhibitors against Aspergillus species in vitro. J Antimicrob Chemother, 2001; 48:775-779. https://doi.org/10.1093/jac/48.6.775

Mitsunobu O. The use of diethyl azodicarboxylate and triphenylphosphine in synthesis and transformation of natural products. Synthesis, 1981; 1:1-28. https://doi.org/10.1055/s-1981-29317

Murali Krishna Kumar M, Madhavi K, Raghuveer Varma P, Risy Namratha J and Purna Nagasree K. Shape based virtual screening and discovery of potential antitubercular agents in non-antibiotics. Int J Drug Design and Disc, 2015; 6:1430-1434.

Mahalakshmi Naidu K, Srinivasarao S, Agnieszka N, Augustynowicz-Kopec Ewa, Murali Krishna Kumar M. Seeking potent anti-tubercular agents: Design, synthesis, anti-tubercular activity and docking study of various (triazoles/indole)-piperazin-1-yl/1,4-diazepan- 1-yl) benzo[d] isoxazole derivatives. Bioorg. Med. Chem. Lett, 2016; 26:2245-2250. https://doi.org/10.1016/j.bmcl.2016.03.059

Martins M, Dastidar SG, Fanning S, Kristiansen JE, Molnar J, Pagès JM, Schelz Z, Spengler G, Viveiros M, Amaral L. Potential role of non-antibiotics (helper compounds) in the treatment of multidrug-resistant Gram-negative infections: mechanisms for their direct and indirect activities. Int J Antimicrob Agents, 2008; 31:198–208. https://doi.org/10.1016/j.ijantimicag.2007.10.025

Munoz-Bellido JL, Munoz-Criado S, Garcı a-Rodrı guezJ A. Antimicrobial activity of psychotropic drugs Selective serotonin reuptake inhibitors. Int J Antimicrobial Agents, 2000; 14:177–180. https://doi.org/10.1016/S0924-8579(99)00154-5

Silvestri R, Artico M, La Regina G, Di Pasquali A, De Martino G, D'Auria FD, Nencioni L, Palamara AT. Imidazole Analogues of Fluoxetine, a Novel Class of Anti-Candida Agents. J Med Chem, 2004; 47:3924–3926. https://doi.org/10.1021/jm049856v

Rastogi N, Goh KS, Wright EL. Potential drug targets for Mycobacterium avium defined by radiometric drug-inhibitor combination techniques. Antimicrob Agents Chemother, 1994; 38:2287-2295. https://doi.org/10.1128/AAC.38.10.2287

Wenthur CJ, Bennett MR, Lindsley CW. Classics in Chemical Neuroscience: Fluoxetine (Prozac). ACS Chemical Neuroscience, 2014; 5:14-23. https://doi.org/10.1021/cn400186j

Willyard C. The drug-resistant bacteria that pose the greatest health threats. Nature, 2017; 543:7643-7648. https://doi.org/10.1038/nature.2017.21550

WHO Global tuberculosis report. 2017. Available at http://www. who.int/.int/tb/publications/global_report/en [Accessed 1 Dec 2017].

Article Metrics
993 Views 78 Downloads 1071 Total

Year

Month

Related Search

By author names