- Novel tdp1 inhibitors based on adamantane connected with monoterpene moieties via heterocyclic fragments
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Tyrosyl-DNA phosphodiesterase 1 (Tdp1) is a promising target for anticancer therapy due to its ability to counter the effects topoisomerase 1 (Top1) poison, such as topotecan, thus, decreasing their efficacy. Compounds containing adamantane and monoterpenoid residues connected via 1,2,4-triazole or 1,3,4-thiadiazole linkers were synthesized and tested against Tdp1. All the derivatives exhibited inhibition at low micromolar or nanomolar concentrations with the most potent inhibitors having IC50 values in the 0.35–0.57 μM range. The cytotoxicity was determined in the HeLa, HCT-116 and SW837 cancer cell lines; moderate CC50 (μM) values were seen from the mid-teens to no effect at 100 μM. Furthermore, citral derivative 20c, α-pinene-derived compounds 20f, 20g and 25c, and the citronellic acid derivative 25b were found to have a sensitizing effect in conjunction with topotecan in the HeLa cervical cancer and colon adenocarcinoma HCT-116 cell lines. The ligands are predicted to bind in the catalytic pocket of Tdp1 and have favorable physicochemical properties for further development as a potential adjunct therapy with Top1 poisons.
- Chepanova, Arina A.,Dyrkheeva, Nadezhda S.,Ilina, Ekaterina S.,Korchagina, Dina V.,Lavrik, Olga I.,Mozhaitsev, Evgenii S.,Munkuev, Aldar A.,Reynisson, Jóhannes,Salakhutdinov, Nariman F.,Suslov, Evgeniy V.,Volcho, Konstantin P.,Zakharenko, Alexandra L.,Zakharova, Olga D.
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- INSECT PHEROMONES AND THEIR ANALOGUES XXXII. CHIRAL PHEROMONES BASED ON (S)-(+)-3,7-DIMETHYLOCTA-1,6-DIENE. 1. SYNTHESIS OF (4R,8RS)-4,8-DIMETHYLDECANAL
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The synthesis of optically active (4R,8RS)-4,8-dimethyldecanal - the aggregation pheromone of the flour beetles Tribolium confusum and T. castaneum - has been effected.The starting compound was the readily available enantiomerically enriched (S)-(+)-3,7-dimethylocta-1,6-diene with an optical purity of ca. 50percent.
- Odinokov, V. N.,Ishmuratov, G. Yu.,Kharisov, R. Ya.,Yakovleva, M. P.,Sultanov, R. M.,et al.
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- Stereoselective Synthesis of the Antileukemic Sesquiterpene (+)-Caparratriene from L-menthol and Tiglic Aldehyde
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A stereoselective synthesis of natural (+)-caparratriene was developed starting from commercially available L-menthol and tiglic aldehyde. The key step was a Wittig reaction of the latter with the triphenylphosphorane generated from (R)-(–)-citronellyl bromide. (+)-Caparratriene as a mixture (4:1) of 2E,4E- and 2E,4Z-stereoisomers is a known anticancer agent.
- Vydrina,Kravchenko,Yakovleva,Ishmuratova,Ishmuratov, G. Yu.
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- Synthesis of novel chiral ionic liquids and their phase behavior in mixtures with smectic and nematic liquid crystals
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Alkylation of 1-alkyl-1H-imidazoles 2a-f with citronellyl bromide 1b opens access to chiral 1H-imidazolium bromides 3a-f (Scheme 1). A similar strategy yielded the chiral pyridinium ionic liquid 6 (Scheme 2). Dialkylation of 1H-imidazole (7) gave the C2-symmetric 1,3-dicitronellyl-1H- imidazolium bromide (8) (Scheme 3). Differential scanning calorimetry and optical polarizing microscopy revealed smectic mesophases for 1-citronellyl-3-tetradecy-1H-limidazolium bromide (3e) and 1- citronellylpyridinium bromide (6) (Table). In binary mixtures with smectic and nematic liquid crystals 9 and 10, 1-citronellyl-3-methyl-1H-imidazolium bromide (3a) behaved differently. Increasing quantities of 3a cause a decrease of the smectic-phase width for the mixture 3a/9 (Fig. 3), whereas the phase width of the nematic phase for 3a/10 remained nearly constant (Fig. 4).
- Tosoni, Martin,Laschat, Sabine,Baro, Angelika
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- Total synthesis of four stereoisomers of methyl 4,8,12-trimethylpentadecanoate, a major component of the sex pheromone of the stink bug: Edessa meditabunda
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The male-produced sex pheromone of the stink bug Edessa meditabunda was previously identified as a mixture of the esters methyl 4,8,12-trimethylpentadecanoate (1) and methyl 4,8,12-trimethyltetradecanoate (2), produced in a ratio of 92 : 8, respectively.
- Schulz, Stefan,Szczerbowski, Daiane,Zarbin, Paulo Henrique Gorgatti
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- New hybrid compounds combining fragments of usnic acid and monoterpenoids for effective tyrosyl-dna phosphodiesterase 1 inhibition
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Usnic acid (UA) is a secondary metabolite of lichens that exhibits a wide range of biological activities. Previously, we found that UA derivatives are effective inhibitors of tyrosyl-DNA phosphodiesterase 1 (TDP1). It can remove covalent complex DNA-topoisomerase 1 (TOP1) stabi-lized by the TOP1 inhibitor topotecan, neutralizing the effect of the drugs. TDP1 removes damage at the 3′ end of DNA caused by other anticancer agents. Thus, TDP1 is a promising therapeutic target for the development of drug combinations with topotecan, as well as other drugs for cancer treatment. Ten new UA enamino derivatives with variation in the terpene fragment and substituent of the UA backbone were synthesized and tested as TDP1 inhibitors. Four compounds, 11a-d, had IC50 values in the 0.23–0.40 μM range. Molecular modelling showed that 11a-d, with relatively short aliphatic chains, fit to the important binding domains. The intrinsic cytotoxicity of 11a-d was tested on two human cell lines. The compounds had low cytotoxicity with CC50 ≥ 60 μM for both cell lines. 11a and 11c had high inhibition efficacy and low cytotoxicity, and they enhanced topotecan’s cyto-toxicity in cancerous HeLa cells but reduced it in the non-cancerous HEK293A cells. This “protec-tive” effect from topotecan on non-cancerous cells requires further investigation.
- Dyrkheeva, Nadezhda S.,Filimonov, Aleksandr S.,Luzina, Olga A.,Zakharenko, Alexandra L.,Ilina, Ekaterina S.,Malakhova, Anastasia A.,Medvedev, Sergey P.,Reynisson, Jóhannes,Volcho, Konstantin P.,Zakian, Suren M.,Salakhutdinov, Nariman F.,Lavrik, Olga I.
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- Synthesis of the 1,5-dimethylic chiron enantiomers, 3,7,11-trimethyldodec-10-en-1-ol: Application to enantiomeric syntheses of tribolure and a marine fatty acid
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A convenient synthesis of the title chiron antipodes has been developed starting from (±)-citronellol via a sequential acetylation protocol using two lipases. The different stereoisomers of the chiron were then functionalized by simple routes to (4R,8R)-dimethyldecanal, an insect pheromone and (5R,9R)-5,9,13-trimethyltetradecanoic acid, a marine phospholipid fatty acid.
- Sankaranarayanan,Sharma, Anubha,Chattopadhyay, Subrata
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- Reassignment of the absolute configuration of plakinidone from the sponge consortium Plakortis halichondrioides-Xestospongia deweerdtae using a combination of synthesis and a chiroptical approach
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Recent work by Wu et al. in connection with the first synthesis of the marine natural product plakinidone revealed that the most salient feature of its purported structure, a six-membered perlactone moiety, was in fact a five-membered lactone, i.e. a 3-me
- Jiménez-Romero, Carlos,Rode, Joanna E.,Rodríguez, Abimael D.
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- Enantiospecific synthesis of 6-methylheptadec-(9E)-enoic acid enantiomers, the antimicrobial principles of Sporothrix species
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An efficient synthesis of the title compound I in both its enantiomeric forms has been developed starting from (R)-citronellol. This involved the introduction of the required alkyl chain and the acidic component at the termini of the starting chiron via judicious derivatization of its bifunctionality to provide the enantiomers of I. The other key features of the synthesis were: (i) use of easily accessible and inexpensive materials/reagents; (ii) operational simplicity; and (iii) brevity.
- Sankaranarayanan, Sivaraman,Chattopadhyay, Subrata
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- Photocatalyic Appel reaction enabled by copper-based complexes in continuous flow
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A copper-based photocatalyst, Cu(tmp)(BINAP)BF4, was found to be active in a photoredox Appel-type conversion of alcohols to bromides. The catalyst was identified from a screening of 50 complexes and promoted the transformation of primary and secondary alcohols to their corresponding bromides and carboxylic acids to their anhydrides. The protocol was also amendable and optimized under continuous flow conditions.
- Minozzi, Clémentine,Grenier-Petel, Jean-Christophe,Parisien-Collette, Shawn,Collins, Shawn K.
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- Custom-Made Pyrene Photocatalyst-Promoted Desulfonylation of Arylethenyl Sulfones Using Green-Light-Emitting Diodes
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The Sonogashira coupling of 1,3,6,8-tetrabromopyrene with 4-[(-)-β-citronellyloxy]phenylethyne was employed to synthesize 1,3,6,8-tetra[4-(citronellyloxy)phenylethynyl]pyrene. The pyrene derivative catalyzed the reductive desulfonylation of ethenyl sulfones via visible-light irradiation (514 nm green light-emitting diodes) in the presence of i -Pr 2NEt. The β-citronellyloxy groups provided the sufficient solubility to the highly π-expanded pyrene catalyst, and their polar oxygen functionalities enabled the easy separation of the catalyst from the products via column chromatography.
- Watanabe, Hikaru,Nakajima, Kazuki,Ekuni, Kento,Edagawa, Ryota,Akagi, Yuta,Okuda, Yasuhiro,Wakamatsu, Kan,Orita, Akihiro
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supporting information
p. 2984 - 2994
(2021/03/04)
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- New chemical agents based on adamantane-monoterpene conjugates against orthopoxvirus infections
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Currently, the spectrum of agents against orthopoxviruses, in particular smallpox, is very narrow. Despite the fact that smallpox is well controlled, there is, for many reasons, a real threat of epidemics associated with this or a similar virus. In order to search for new low molecular weight orthopoxvirus inhibitors, a series of amides combining adamantane and monoterpene moieties were synthesized using 1- and 2-adamantanecarboxylic acids as well as myrtenic, citronellic and camphorsulfonic acids as acid components. The produced compounds exhibited high activity against the vaccinia virus (an enveloped virus belonging to the poxvirus family), which was combined with low cytotoxicity. Some compounds had a selectivity index higher than that of the reference drug cidofovir; the highest SI = 1123 was exhibited by 1-adamantanecarboxylic acid amide containing the (-)-10-amino-2-pinene moiety. The produced compounds demonstrated inhibitory activity against other orthopoxviruses: cowpox virus (SI = 30-406) and ectromelia virus (mousepox virus, SI = 39-707). This journal is
- Agafonov, Alexander P.,Bormotov, Nikolay I.,Korchagina, Dina V.,Maksyutov, Rinat A.,Mozhaytsev, Evgenii S.,Salakhutdinov, Nariman F.,Serova, Olga A.,Shishkina, Larisa N.,Suslov, Evgenii V.,Volcho, Konstantin P.,Yarovaya, Olga I.
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p. 1185 - 1195
(2020/11/03)
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- The first blue phase reactive monomers containing a bi-mesogenic core and their side-chain polymers
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Two novel blue phase (BP) reactive monomers M1 and M2 containing a bi-mesogenic core are first reported by introducing two end-attached acrylic spacers with different lengths. Due to the self-assembly of bi-mesogenic cores with the same side-by-side end-attached acrylate spacers in homopolymers P1 and P2, no blue phase could be induced by homopolymerization of M1 and M2. However, by interrupting the self-assembly of bi-mesogenic cores with different side-by-side spacer lengths of copolymers P12, double-twisted cylinders of BPIII could be further extended by copolymerization of M1 and M2 with different molar ratios. With M1:M2 = 5:5 (molar ratio) in both side-chain copolymers P12(soln:5/5) and P12(photo:5/5) rather than binary mixture M1/M2(5/5), the widest BPIII ranges of 5.3 °C and 3.8 °C could be obtained by solution- and photo-polymerization, respectively.
- Wei, Chong-Lun,Lin, Yen-Ting,Chang, Jin-Huai,Chiang, I-Hung,Lin, Hong-Cheu
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supporting information
p. 4663 - 4669
(2015/12/05)
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- Novel asymmetrical single- and double-chiral liquid crystal diads with wide blue phase ranges
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In this study, two series of novel asymmetrical single- and double-chiral liquid crystal diads using a central linker to link two different mesogenic cores were successfully synthesized. The effects of the position of chiral centers and the number of aromatic rings on the mesomorphic and electro-optical properties were investigated. We found that diads III-N (where N = A, B, C and D) have better mesophasic properties than II-N (where N = A, B, C, D and E). Compared with III-C with a chiral center at the terminal alkoxyl chain, diad III-D exhibited the widest temperature range of BPI (ca. 31°C) as the chiral center was introduced to the central linker. Besides III-D, BPs were also observed in diads II-B and III-B with a chiral center at the central spacer. According to our experimental results and molecular modeling, the mesomorphic properties and temperature ranges of BPs will be affected by the values of biaxiality and dipole moment, along with the bent shape of molecular geometry. Therefore, we demonstrated the first example of asymmetrical single- and double-chiral liquid crystal diads involved chiral centers located at the central linker to exhibit BPs, including the mesophases of BPI and BPIII, which might offer new BP single-components to the future applications of eutectic liquid crystal mixtures with wide BP ranges.
- Wei, Chong-Lun,Chen, Te-Cheng,Raghunath, Putikam,Lin, Ming-Chang,Lin, Hong-Cheu
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p. 4615 - 4622
(2015/02/19)
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- Chiral tetraphenylethenes as novel dopants for calamitic and discotic liquid crystals
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Three series of novel chiral tetraphenylethenes have been prepared: citronellyl-derived ethers 1a, b, lactate-derived ethers 2d, g, h, i and lactate-derived esters 3a-c, e-h. Helical twisting powers (HTPs) were determined for those derivatives of 1-3, whi
- Schreivogel, Alina,Dawin, Ute,Baro, Angelika,Giesselmannb, Frank,Laschat, Sabine
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scheme or table
p. 484 - 494
(2010/04/05)
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- Novel synthetic approach to 19-nor-1α,25-dihydroxyvitamin D3 and its derivatives by Suzuki-Miyaura coupling in solution and on solid support
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equation presented 19-nor-1α,25-Dihydroxyvitamin D3 was synthesized by the Suzuki-Miyaura coupling of the A-ring intermediate 3, which was efficiently prepared from readily available 5-(tert-butyldimethylsilyl)oxycyclohex-2-enone (5), with the
- Hanazawa, Takeshi,Wada, Takeshi,Masuda, Tomoko,Okamoto, Sentaro,Sato, Fumie
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p. 3975 - 3977
(2007/10/03)
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- Synthesis of the spiroacetal parts of spirofungin A and B
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The C9-C20 spiroacetal parts of spirofungin A and B, antifungal antibiotics from Streptomyces violaceusniger Tu 4113, were synthesized simultaneously from (S)-citronellyl bromide and (±)-epoxy alcohol via alkyne-lactone coupling reaction and diastereomeric separation. (C) 2000 Elsevier Science Ltd.
- Shimizu, Yuko,Kiyota, Hiromasa,Oritani, Takayuki
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p. 3141 - 3144
(2007/10/03)
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- Synthesis of (1S,2R,12S)-2-hydroxy-11-dihydroneocembrene
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Aiming at the asymmetric total synthesis of trinervitane-type diterpenes, an efficient synthetic route to the title compound was explored starting from the THP ether of pivaloyloxy geraniol 11e. The coupling reaction with Grignard reagent 14 bearing the s
- Kato, Tadahiro,Ebihara, Shin-Ichi,Furukawa, Tohru,Tanahashi, Hirota,Hoshikawa, Masahiro
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p. 3691 - 3700
(2007/10/03)
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- A convenient synthesis of (4R,7Z,11Z)-(-)-4-methylheptadeca-7,11-dienal and (4R,7Z,11Z)-4-methylheptadeca-7,11-dienoic acid
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A synthesis of the title aldehyde 1 and acid 2, the (R) enantiomers of the antifungal and antibacterial principles of Sporothrix species, was developed. Alkylation of the alkynol derivative 6 with (S)-citronellyl bromide (5), depyranylation, cis hydrogenation, PCC oxidation, and Z-selective Wittig reaction with hexylidenephosphorane gave the hydrocarbon 11. Its regioselective epoxidation and cleavage of the epoxide with HlO4 affords (R)-1 which was oxidized to (R)-2. VCH Verlagsgesellschaft mbH, 1996.
- Sharma, Anubha,Chattopadhyay, Subrata
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p. 529 - 531
(2007/10/03)
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- OZONOLYSIS OF ALKENES AND REACTIONS OF POLYFUNCTIONAL COMPOUNDS. XLVI. SYNTHESIS OF (4S,8S)-4,8-DIMETHYLDECANAL AND ITS DIMETHYL ACETAL
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From accessible chiral structural blocks, namely, (R)-methyl-citronellate and (S)-2-methyl-1-butanol, (6S,10S)-2,6,10-trimethyl-2-dodecene was synthesized.The ozonolysis of this gave (4S,8S)-4,8-dimethyldecanal, one of the stereoisomers of the aggregation pheromone of the meal worms Tribolium confusium and T. castaneum, and its dimethyl acetal.
- Odinokov, V. N.,Akhmetova, V. R.,Khasanov, Kh. D.,Abduvakhabov, A. A.,Sul'tanmuratova, V. R.,Tolsikov, G. A.
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p. 915 - 918
(2007/10/02)
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- Chiral Synthesis of Trogodermal, the Pheromone of Dermestid Beetles
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The title pheromone, (R)-14-methyl-8-(Z and E)-hexadecen-1-al (Ia and Ib) have been synthesised following a simple route using (R)-pulegone as the starting chiron.
- Chattopadhyay, S.,Mamdapur, V.R.,Chadha, M.S.
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p. 825 - 837
(2007/10/02)
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