Antimycobacterial activity of chiral aminoalcohols with camphane scaffold

Petkova, Zhanina; Valcheva, Violeta; Momekov, Georgi; Petrov, Petar; Dimitrov, Vladimir; Doytchinova, Irini; Stavrakov, Georgi; Stoyanova, Malinka

doi:10.1016/j.ejmech.2014.05.007

Cited by 16 publications

(13 citation statements)

References 12 publications

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“…Monoterpenoid‐based agent SQ 109 (Figure ), combining 2‐adamantylamine and geranylamine, is a novel anti‐TB drug candidate with a unique multimodal mechanism of action . Recently, we have reported a series of studies focused on the synthesis of antituberculosis agents containing the bicyclo[2.2.1]heptane framework fragment . The latter is combined with a number of pharmacophore groups resulting in improved physiological and pharmacological properties.…”

Section: Introductionmentioning

confidence: 99%

Synthetic piperine amide analogs with antimycobacterial activity

et al. 2017

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Piperine amide analogs are synthesized by replacement of the piperidine moiety with different types of cyclic amines, including adamantyl and monoterpene-derived fragments. The compounds are screened for activity against Mycobacterium tuberculosis H37Rv. The most potent compounds are the 1-adamantyl and the monoterpene-derived hybrids, which combine nanomolar antimycobacterial activity with low cytotoxicity against human cells. The presence of quaternary carbon atom as main structural requirement for anti-TB activity is pointed out by a QSAR study. The most promising compound is the (+)-isopinocampheylamine-derived amide which is characterized with selectivity index of 1387.8.

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Section: Introductionmentioning

confidence: 99%

Synthetic piperine amide analogs with antimycobacterial activity

et al. 2017

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“…Surgical excision and reconstruction are often required in very serious cases. Atypical Mycobacterium infections can be treated with a variety of antibiotics, although treatment is difficult, due to these organisms often being resistant to regular TB medication [25,38,7,13,44,46,14,107,111,56,20].…”

Section: Discussionmentioning

confidence: 99%

“…Phase one treatment consists of INH, RIF, EMB and PZA for 2 months, followed by 4 months' treatment with INH and RIF in phase two. If INH resistance is suspected, EMB can also be given in phase two [22,6,47,38,13,14,29,65,56,34,20,35,30].…”

Section: True Cutaneous Tuberculosis and Tuberculidsmentioning

confidence: 99%

Cutaneous tuberculosis overview and current treatment regimens

2015

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“…Among the synthesized compounds, N -geranyl- N ′-(2-adamanthan-1-yl)ethane-1,2-diamine ( Figure 1 c) showed promising efficiency [ 12 ]. The outlined systematic research led to N -ArPA molecules ( Figure 1 d), in which structure the distance between two nitrogens, presence of β -aminoalcohol motifs and short connecting chains were crucial for their in vitro antimycobacterial activity [ 13 ]. The derivatives N -ArPA were very effective against Mycobacterium tuberculosis CNCTC My 331/88 (identical with M. tuberculosis H 37 R v ) and multi-drug resistant (MDR) M. tuberculosis 43 strain, which showed resistance to rifampicin (RIF) and isoniazid (INH).…”

Section: Introductionmentioning

confidence: 99%

“…It was also concluded that removal or significant alteration of basicity of either amino group led to loss of potency [ 9 , 13 ]. In addition, the presence of the R = 2-/4-F substituent and OH group with the ( R )-configuration at the carbon of a connecting chain ( Figure 1 d) resulted in higher in vitro antimycobacterial efficiency than in a case of EMB.…”

Section: Introductionmentioning

confidence: 99%

Synthesis and In Vitro Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain

et al. 2017

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Novel 1-(2-{3-/4-[(alkoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)-piperazin-1-ium chlorides (alkoxy = methoxy to butoxy; 8a–h) have been designed and synthesized through multistep reactions as a part of on-going research programme focused on finding new antimycobacterials. Lipophilic properties of these compounds were estimated by RP-HPLC using methanol/water mobile phases with a various volume fraction of the organic modifier. The log kw values, which were extrapolated from intercepts of a linear relationship between the logarithm of a retention factor k (log k) and volume fraction of a mobile phase modifier (ϕM), varied from 2.113 (8e) to 2.930 (8h) and indicated relatively high lipophilicity of these salts. Electronic properties of the molecules 8a–h were investigated by evaluation of their UV/Vis spectra. In a next phase of the research, the compounds 8a–h were in vitro screened against M. tuberculosis CNCTC My 331/88 (identical with H37Rv and ATCC 2794), M. kansasii CNCTC My 235/80 (identical with ATCC 12478), a M. kansasii 6 509/96 clinical isolate, M. avium CNCTC My 330/80 (identical with ATCC 25291) and M. avium intracellulare ATCC 13950, respectively, as well as against M. kansasii CIT11/06, M. avium subsp. paratuberculosis CIT03 and M. avium hominissuis CIT10/08 clinical isolates using isoniazid, ethambutol, ofloxacin, ciprofloxacin or pyrazinamide as reference drugs. The tested compounds 8a–h were found to be the most promising against M. tuberculosis; a MIC = 8 μM was observed for the most effective 1-(2-{4-[(butoxycarbonyl)amino]phenyl}-2-hydroxyethyl)-4-(2-fluorophenyl)piperazin-1-ium chloride (8h). In addition, all of them showed low (insignificant) in vitro toxicity against a human monocytic leukemia THP-1 cell line, as observed LD50 values > 30 μM indicated. The structure–antimycobacterial activity relationships of the analyzed 8a–h series are also discussed.

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Antimycobacterial activity of chiral aminoalcohols with camphane scaffold

Cited by 16 publications

References 12 publications

Synthetic piperine amide analogs with antimycobacterial activity

Synthetic piperine amide analogs with antimycobacterial activity

Cutaneous tuberculosis overview and current treatment regimens

Synthesis and In Vitro Antimycobacterial Activity of Novel N-Arylpiperazines Containing an Ethane-1,2-diyl Connecting Chain

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