Concise synthesis of stereodefined, thiazole—containing cyclic hexa- and octapeptide relatives of the Lissoclinums, via cyclooligomerisation reactions

Bertram, Anna; Blake, Alexander J.; Turiso, Felix González-López de; Hannam, Jeffery S.; Jolliffe, Katrina A.; Pattenden, Gerald; Skae, Michael

doi:10.1016/s0040-4020(03)00821-4

Cited by 42 publications

(28 citation statements)

References 37 publications

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“…The thiazole derivatives were synthesized with diminutive variations in the procedures reported by Bertram et al and as shown in Schemes 1 to 6. [19,20] Compounds with one thiazole unit, both linear and cyclic, are referred to as monomeric derivatives, those with two thiazole units are called dimeric, and so forth (trimeric, tetrameric, and hexameric). Scheme 1 shows the synthesis of monomeric derivatives, starting with commercially available N-Boc-(S)-valine (1), which was converted to amide 2 by a general mixed anhydride/aqueous ammonia method in quantitative yield (Scheme 1).…”

Section: Chemistrymentioning

confidence: 99%

“…Compound 18 was prepared by coupling 10 and 11; linear hexamer 19 was synthesized beginning from 14 and 15. The cyclic tetramer (20) and cyclic hexamer (21) were synthesized starting from dimer zwitterion (12), giving both products in one step (Scheme 5). The tetramer and hexamer derivatives were produced in very low yields (Schemes 4 and 5); therefore, the desired products were purified and characterized by means of preparative HPLC with subsequent electron spray ionization-mass spectrometry (ESI-MS) analysis.…”

Section: Chemistrymentioning

confidence: 99%

“…The synthesized (S)-valine-derived thiazole products (5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(17)(18)(19)(20)(21)(22)(23) were evaluated for their effect on human P-gp activity utilizing multiple assays. Table 1 represents the percent inhibition values for all thiazole derivatives obtained from calcein-AM and BODIPY-FL-Prazosin efflux assays in HeLa cells expressing human P-gp.…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

“…Functionally, P-gp possesses ATPase activity that is stimulated by many substrates. [33,34] ATPase stimulation activity for selected derivatives (13)(14)(15)(17)(18)(19)(20)(21)(22)(23) was determined by using membranes of P-gp-expressing High-Five insect cells (Table 3). Here as well, the linear (13, fold stimulation = 2.80) and the cyclic (17, fold stimulation = 2.81) trimer analogues were found to stimulate the ATPase activity equivalently.…”

Section: Structure-activity Relationshipsmentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of (S)‐Valine Thiazole‐Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P‐Glycoprotein (ABCB1)

et al. 2013

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Multidrug resistance (MDR) caused by ATP-binding cassette (ABC) transporter P-glycoprotein (P-gp) through extrusion of anticancer drugs from the cells is a major cause of failure to cancer chemotherapy. Previously, selenazole containing cyclic peptides were reported as P-gp inhibitors and these were also used for co-crystallization with mouse P-gp, which has 87% homology to human P-gp. It has been reported that human P-gp, can simultaneously accommodate 2-3 moderate size molecules at the drug binding pocket. Our in-silico analysis based on the homology model of human P-gp spurred our efforts to investigate the optimal size of (S)-valine-derived thiazole units that can be accommodated at drug-binding pocket. Towards this goal, we synthesized varying lengths of linear and cyclic derivatives of (S)-valine-derived thiazole units to investigate the optimal size, lipophilicity and the structural form (linear and cyclic) of valine-derived thiazole peptides that can accommodate well in the P-gp binding pocket and affects its activity, previously an unexplored concept. Among these oligomers, lipophilic linear- (13) and cyclic-trimer (17) derivatives of QZ59S-SSS were found to be the most and equally potent inhibitors of human P-gp (IC50 = 1.5 μM). Cyclic trimer and linear trimer being equipotent, future studies can be focused on non-cyclic counterparts of cyclic peptides maintaining linear trimer length. Binding model of the linear trimer (13) within the drug-binding site on the homology model of human P-gp represents an opportunity for future optimization, specifically replacing valine and thiazole groups in the non-cyclic form.

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Section: Chemistrymentioning

confidence: 99%

Section: Chemistrymentioning

confidence: 99%

Section: Structure-activity Relationshipsmentioning

confidence: 99%

Section: Structure-activity Relationshipsmentioning

confidence: 99%

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Design, Synthesis, and Biological Evaluation of (S)‐Valine Thiazole‐Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P‐Glycoprotein (ABCB1)

et al. 2013

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“…5 Cyclopeptides containing thiazole and dihydrothiazole rings also have cytotoxic activity. [6][7][8][9] Moreover, a number of 2-thiazolylhydrazones have shown mitochondrial monoamine oxidase inhibitory (MAOI) activity, 10 antibacterial activities against S. aureus and P. aeruginosa, 11 and antifungal activities against C. albicans and C. krusei. 12 Therefore, we report herein the synthesis and antimicrobial activity of novel [4-(4- …”

Section: Introductionmentioning

confidence: 99%

Synthesis of Biologically Active [4‐(4‐Bromophenyl)‐2‐thiazolyl]hydrazones and their D‐Galactose Derivatives

Ramadan¹

2010

Chin. J. Chem.

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Benzaldehyde [4-(4-bromophenyl)thiazol-2-yl]hydrazones 5a-5d were prepared by reacting the thiosemicarbazones 2a-2d with 2,4'-dibromoacetophenone (1) in absolute ethanol. Acetylation of 5a and 5b with Ac 2 O/Py at room temperature gave the N-acetyl derivatives 6a and 6b. 4-Methyl-2-pentanone/cyclopentanone [4-(4-bromophenyl)thiazol-2-yl]hydrazones (8a) and (8b) were similarly obtained from the reaction of 1 with the thiosemicarbazones 7a and 7b, respectively. Cyclization of D-galactose thiosemicarbazone (9) and its tautomers 10 and 11 with 1 afforded an equilibrium mixture of the acyclic 2-thiazolylhydrazone 12, together with its respective cyclic galactosyl derivatives 13 and 14, whose structures were studied by using 1 H and 13 C NMR spectra. The antimicrobial activity of the synthesized thiazole derivatives was evaluated in vitro by using an agar diffusion technique, and some of these compounds showed potential activity against Candida albicans.

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Other Five‐Membered Heterocycles

Li¹,

Corey²

2004

Name Reactions in Heterocyclic Chemistry

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Concise synthesis of stereodefined, thiazole—containing cyclic hexa- and octapeptide relatives of the Lissoclinums, via cyclooligomerisation reactions

Cited by 42 publications

References 37 publications

Design, Synthesis, and Biological Evaluation of (S)‐Valine Thiazole‐Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P‐Glycoprotein (ABCB1)

Design, Synthesis, and Biological Evaluation of (S)‐Valine Thiazole‐Derived Cyclic and Noncyclic Peptidomimetic Oligomers as Modulators of Human P‐Glycoprotein (ABCB1)

Synthesis of Biologically Active [4‐(4‐Bromophenyl)‐2‐thiazolyl]hydrazones and their D‐Galactose Derivatives

Other Five‐Membered Heterocycles

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