N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity

Niranjan Thota, Parameshwar Makam, Kamal K. Rajbongshi, Savania Nagiah, Naeem Sheik Abdul, Anil A. Chuturgoon, Amit Kaushik, Gyanu Lamichhane, Anou M. Somboro, Hendrik G. Kruger, Thavendran Govender, Tricia Naicker, Per I. Arvidsson

Research output: Contribution to journalArticle

Abstract

Herein we demonstrate the expanded utility of a recently described N-trifluoromethylthiolation protocol to sulfonimidamide containing substances. The novel N-trifluoromethylthio sulfonimidamide derivatives thus obtained were evaluated for antibacterial activity against Mycobacterium tuberculosis (M. tb.) and Mycobacterium abscessus and Gram + Ve (Streptococcus aureus, Bacillus subtilis), and Gram - Ve (Escherichia coli, Pseudomonas aeruginosa) bacteria. Two compounds, 13 and 15 showed high antimycobacterial activity with MIC value of 4-8 μg/mL; i.e. comparable to WHO recommended first line antibiotic for TB infection ethambutol. The same compounds were also found to be cytotoxic in HepG2 cells (compound 13 IC50 = 15 μg/mL; compound 15 IC50 = 65 μg/mL). A structure activity relationship, using matched pair analysis, gave the unexpected conclusion that the trifluoromethylthio moiety was responsible for the cellular and bacterial toxicity. Given the increasing use of the trifluoromethylthio group in contemporary medicinal chemistry, this observation calls for considerations before implementation of the functionality in drug design.

Original languageEnglish (US)
Pages (from-to)1457-1461
Number of pages5
JournalACS Medicinal Chemistry Letters
Volume10
Issue number10
DOIs
StatePublished - Oct 10 2019

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Ethambutol
Bacilli
Escherichia coli
Inhibitory Concentration 50
Toxicity
Bacteria
Anti-Bacterial Agents
Derivatives
Matched-Pair Analysis
Pharmaceutical Chemistry
Drug Design
Hep G2 Cells
Structure-Activity Relationship
Mycobacterium
Streptococcus
Bacillus subtilis
Mycobacterium tuberculosis
Pharmaceutical Preparations
Pseudomonas aeruginosa
Infection

Keywords

  • cytotoxicity
  • drug discovery
  • medicinal chemistry
  • Mycobacterium abscessus
  • Mycobacterium tuberculosis
  • Sulfonimidamide
  • Trifluoromethylthio

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

Cite this

Thota, N., Makam, P., Rajbongshi, K. K., Nagiah, S., Abdul, N. S., Chuturgoon, A. A., ... Arvidsson, P. I. (2019). N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity. ACS Medicinal Chemistry Letters, 10(10), 1457-1461. https://doi.org/10.1021/acsmedchemlett.9b00285

N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines : Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity. / Thota, Niranjan; Makam, Parameshwar; Rajbongshi, Kamal K.; Nagiah, Savania; Abdul, Naeem Sheik; Chuturgoon, Anil A.; Kaushik, Amit; Lamichhane, Gyanu; Somboro, Anou M.; Kruger, Hendrik G.; Govender, Thavendran; Naicker, Tricia; Arvidsson, Per I.

In: ACS Medicinal Chemistry Letters, Vol. 10, No. 10, 10.10.2019, p. 1457-1461.

Research output: Contribution to journalArticle

Thota, N, Makam, P, Rajbongshi, KK, Nagiah, S, Abdul, NS, Chuturgoon, AA, Kaushik, A, Lamichhane, G, Somboro, AM, Kruger, HG, Govender, T, Naicker, T & Arvidsson, PI 2019, 'N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines: Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity', ACS Medicinal Chemistry Letters, vol. 10, no. 10, pp. 1457-1461. https://doi.org/10.1021/acsmedchemlett.9b00285
Thota, Niranjan ; Makam, Parameshwar ; Rajbongshi, Kamal K. ; Nagiah, Savania ; Abdul, Naeem Sheik ; Chuturgoon, Anil A. ; Kaushik, Amit ; Lamichhane, Gyanu ; Somboro, Anou M. ; Kruger, Hendrik G. ; Govender, Thavendran ; Naicker, Tricia ; Arvidsson, Per I. / N-Trifluoromethylthiolated Sulfonimidamides and Sulfoximines : Anti-microbial, Anti-mycobacterial, and Cytotoxic Activity. In: ACS Medicinal Chemistry Letters. 2019 ; Vol. 10, No. 10. pp. 1457-1461.
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