- Synthesis and structure insights of two novel broad-spectrum antibacterial candidates based on (E)-N0-[(Heteroaryl)methylene]adamantane-1carbohydrazides
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Two new N0-heteroarylidene-1-carbohydrazide derivatives, namely; E-N0-[(pyridine-3yl)methylidene]adamantane-1-carbohydrazide (1) and E-N0-[(5-nitrothiophen-2-yl)methylidene] adamantane-1-carbohydrazide (2), were produced v
- Al-Mutairi, Aamal A.,Al-Wahaibi, Lamya H.,Alvarez, Natalia,Blacque, Olivier,El-Emam, Ali A.,Veiga, Nicolás
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- Novel antitumor adamantane-azole gold(I) complexes as potential inhibitors of thioredoxin reductase
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Gold complexes that could act as antitumor agents have attracted great attention. Heterocyclic compounds and their metal complexes display a broad spectrum of pharmacological properties. The present study reports the preparation and characterization of fo
- Garcia, Adriana,Machado, Rafael Carvalhaes,Grazul, Richard Michael,Lopes, Miriam Teresa Paz,Corrêa, Charlane Cimini,Dos Santos, Hélio F.,De Almeida, Mauro Vieira,Silva, Heveline
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- In-silico identification of the binding mode of synthesized adamantyl derivatives inside cholinesterase enzymes
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Aim: To investigate the binding mode of synthesized adamantly derivatives inside of cholinesterase enzymes using molecular docking simulations. Methods: A series of hybrid compounds containing adamantane and hydrazide moieties was designed and synthesized
- Al-Aboudi, Amal,Al-Qawasmeh, Raed A.,Shahwan, Alaa,Mahmood, Uzma,Khalid, Asaad,Ul-Haq, Zaheer
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- Synthesis, in vitro cytotoxic and apoptotic effects, and molecular docking study of novel adamantane derivatives
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[4-(Adamantane-1-carboxamido)-3-oxo-1-thia-4-azaspiro[4.4]nonan-2-yl]acetic acid (4a) and [4-(adamantane-1-carboxamido)-8-nonsubstituted/substituted-3-oxo-1-thia-4-azas-piro[4.5]decane-2-yl]acetic acid (4b–g) derivatives were synthesized; their structures were verified by elemental analysis, infrared spectroscopy, 1H nuclear magnetic resonance (NMR), 13C NMR, and mass?spectroscopy data; and their in vitro cytotoxicity activities were investigated against human hepatocellular carcinoma, human prostate adenocarcinoma, and human lung carcinoma cell lines (HepG2, PC-3, and A549, respectively), and a mouse fibroblast cell line (NIH/3T3). All compounds, except?compound 4e, were found as cytotoxic, especially on A549 cells as compared with the other cells (selectivity index = 2.01–11.6). As a further step, the effects of compounds 4a–c on apoptosis induction were tested and the expression of selected apoptosis genes was analyzed. Among the selected compounds, compound 4a induced apoptosis remarkably. Moreover, computational calculations of the binding of compounds 4a–c to the BIR3 domain of the human inhibitor of apoptosis protein revealed ligand–protein interactions at the atomistic level and emphasized the importance of a hydrophobic moiety on the ligands for better binding.
- Turk-Erbul, Basak,Karaman, Ecem F.,Duran, Gizem N.,Ozbil, Mehmet,Ozden, Sibel,Goktas, Fusun
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- Novel adamantane-pyrazole and hydrazone hybridized: Design, synthesis, cytotoxic evaluation, SAR study and molecular docking simulation as carbonic anhydrase inhibitors
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A series of pyrazole derivatives 4, 5, 6, 12, 13, 14 as well as hydrazone derivatives 7, 10, 11 were synthesized starting from adamantane-1-carbohydrazide as the bioactive core. All newly designed adamantane derivates were established by full characterized using different spectroscopic methods. The novel derivatives were investigated for their antitumor activity against three cell line MCF-7, HepG-2 and A549. They displayed good IC50 values ranged between 1.55 to 42.17 μM in comparison to Doxorubicin (IC50 =3.58–8.19 μM). Surprisingly, adamantine derivatives revealed more sensitivity and selectivity to lung cancer cells (A549) with eight compounds (4, 5, 9a, 9b, 9c, 12, 13a and 14c) having IC50 less than or equal ten micromoles. The most promising three adamantane derivatives 9a, 12 and 13a with IC50 values less than 5 μM were selected to study enzymatic assay for isoenzyme hCAIX and hCAXII. Also, pyrazole core 13a and 12 showed higher KI values than hydrazone derivatives 9a with submicromolar between (0.085–0.527 μM), in comparison to Acetazolamide (0.041–0.068 μM). Compound 13a is the most promising derivatives with anti-proliferative (A549) (IC50=1.55 ± 0.08 μM) which showed CAIX/XII inhibitory activity (KI = 0.085 and 0.14 μM), respectively. Finally, molecular docking simulation was performed to determine the binding modes and possible interaction of the adamantane derivatives within the active site of 3IAI and 1JD0 for CAIX / XII respectively with low binding affinity.
- Ammar, Yousry A.,Elhag Ali, Gameel A. M.,Mehany, Ahmed B. M.,Ragab, Ahmed,Wassel, Mohammed M. S.
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- Synthesis and bioactivity of hydrazide-hydrazones with the 1-adamantyl-carbonyl moiety
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Reaction of 1-adamantyl carbohydrazide (1) with various substituted benzaldehydes and acetophenones yielded the corresponding hydrazide-hydrazones with a 1-adamantane carbonyl moiety. The new synthesized compounds were tested for activities against some Gram-negative and Gram-positive bacteria, and the fungus Candida albicans. Compounds 4a, 4b, 5a, and 5c displayed potential antibacterial activity against tested Gram-positive bacteria and C. albicans, while compounds 4e and 5e possessed cytotoxicity against tested human cancer cell lines.
- Pham, Van Hien,Phan, Thi Phuong Dung,Phan, Dinh Chau,Vu, Binh Duong
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- Schiff Bases of Isatin and Adamantane-1-Carbohydrazide: Synthesis, Characterization and Anticonvulsant Activity
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Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18-23). Then, their anticonvulsant activity was evaluated using pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18-23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy with compound 23 being the best. Interestingly, most of the synthesized molecules showed reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.
- Osman, Hind M.,Elsaman, Tilal,Yousef, Bashir A.,Elhadi, Esraa,Ahmed, Aimun A. E.,Eltayib, Eyman Mohamed,Mohamed, Malik Suliman,Mohamed, Magdi Awadalla
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- FLOW CHEMISTRY SYNTHESIS OF ISOCYANATES
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The disclosure provides, inter alia, safe and environmentally-friendly methods, such as flow chemistry, to synthesize isocyanates, such as methylene diphenyl diisocyanate, toluene diisocyanate, hexamethylene diisocyanate, isophorone diisocyanate, and tetramethylxylene diisocyanate.
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Paragraph 0175; 0186-0187; 0360; 0363-0364
(2021/06/22)
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- Facile synthesis and antimycobacterial activity of isoniazid, pyrazinamide and ciprofloxacin derivatives
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Several rationally designed isoniazid (INH), pyrazinamide (PZA) and ciprofloxacin (CPF) derivatives were conveniently synthesized and evaluated in vitro against H37Rv Mycobacterium tuberculosis (M. tb) strain. CPF derivative 16 displayed a modest activity
- Alsayed, Shahinda S. R.,Lun, Shichun,Payne, Alan,Bishai, William R.,Gunosewoyo, Hendra
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p. 1137 - 1150
(2021/03/18)
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- Synthesis and Evaluation of Nifurtimox–Adamantane Adducts with Trypanocidal Activity
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The synthesis and pharmacological evaluation of C1-substituted adamantane hydrazones, their C2-substituted isomers, and C1-substituted adamantane furanoic carboxamides is described. These new adamantane derivatives exhibited an interesting pharmacological profile in terms of trypanocidal activity and selectivity. The most active adduct with the best selectivity in this study was found to be the phenylacetoxy hydrazone 1 b (2-[4-(tricyclo[3.3.1.13,7]dec-1-yl)phenyl]-N′-[(5-nitrofuran-2-yl)methylene]acetohydrazide; EC50=11±0.9 nm, SITb=770).
- Foscolos, Angeliki-Sofia,Papanastasiou, Ioannis,Tsotinis, Andrew,Taylor, Martin C.,Kelly, John M.
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supporting information
p. 1227 - 1231
(2019/07/09)
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- Synthesis, Structure, and Anti-influenza Activity of 2-(Adamantan-1-yl)-5-aryl-1,3,4-oxadiazoles and 2-(Adamantan-1-yl)-5-aryltetrazoles
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Two series of new adamantyl derivatives of polynitrogen heterocycles, 2-(adamantan-1-yl)-5-aryl- 1,3,4-oxadiazoles and 2-(adamantan-1-yl)-5-aryl-2H-tetrazoles, have been synthesized, and their structure has been determined by NMR spectroscopy, mass spectr
- Seliverstova,Suslonov,Zarubaev,Trifonov
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p. 633 - 638
(2018/06/12)
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- New hydrazones of 5-nitro-2-furaldehyde with adamantanealkanohydrazides: Synthesis and: In vitro trypanocidal activity
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Nifurtimox, a hydrazone of 5-nitro-2-furaldehyde is used therapeutically against Trypanosoma brucei and Trypanosoma cruzi infections. Exploiting our previous observation that adamantane derivatives display trypanocidal activity, we designed and synthesised a range of hydrazones of 5-nitro-2-furaldehyde with adamantane alkanohydrazides. The most promising compounds had >20 times greater activity (IC50 ~ 100 nM) than nifurtimox, with selectivity indices of 20-80. SAR studies revealed that activity is associated with increased lipophilicity and influenced by conformational flexibility. Derivatives lacking a nitro group were practically inactive against both parasites. The approaches described demonstrate the feasibility of enhancing the potency of chemical entities with known trypanocidal activity.
- Foscolos, Angeliki-Sofia,Papanastasiou, Ioannis,Foscolos, George B.,Tsotinis, Andrew,Kellici, Tahsin F.,Mavromoustakos, Thomas,Taylor, Martin C.,Kelly, John M.
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supporting information
p. 1229 - 1236
(2016/07/06)
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- Ultrasound-assisted, convenient and widely applicable 1,1′-carbonyl-diimidazole-mediated "One-pot" syntheses of acyl/sulfonyl hydrazines
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Acyl / sulfonyl hydrazines were synthesized in a one-pot reaction from carboxylic acid/aryl sulfonic acid in the presence of 1,1′-carbonyl diimidazole (CDI) under ultrasound as well as under conventional heating. The reaction was performed on diverse organic molecules including simple benzoic acid (1), electron-donating and electron-withdrawing substituted benzoic acids, biologically active compounds like coumarin-3-carboxylic acid (12), 7-hydroxycoumarin-4-acetic acid (13), and therapeutic drugs like ibuprofen (14), flurbiprofen (15), naproxen (16) or tricyclic adamantane carboxylic acid (17). Benzene sulfonic acid (18) and its derivatives (19, 20, 21 and 22) were used to prepare corresponding sulfonyl hydrazide. All products were synthesized in very good yield via ultrasonic irradiation method and characterized by spectroscopic techniques including EIMS, 1H NMR, 13C NMR, IR. The method was found very simple, facile, efficient and high yielding (>90).
- Khan, Khalid Mohammed,Salar, Uzma,Fakhri, Muhammad Imran,Taha, Muhammad,Hameed, Abdul,Perveen, Shahnaz,Voelter, Wolfgang
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p. 637 - 644
(2015/11/09)
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- Microwave-assisted synthesis of new adamantyltriazine derivatives
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The synthesis of new 2-adamantyl-1,2,4-triazine derivatives is described utilizing both, conventional and microwave methods and were obtained in good yields. The proposed structures of the adamantyltriazines were characterized using MS, 1H NMR
- Al-Qawasmeh, Raed A.,Salameh, Bader A.,Alrazim, Rami,Aldamen, Murad A.,Voelter, Wolfgang
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p. 513 - 518
(2014/05/20)
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- Synthesis and antimicrobial activity of novel 5-(1-adamantyl)-2- aminomethyl-4-substituted-1,2,4-triazoline-3-thiones
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The reaction of 5-(1-adamantyl)-4-substituted-1,2,4-triazoline-3-thione 5a,b and 10a,b with formaldehyde solution and various primary aromatic amines or 1-substituted piperazines yielded the corresponding N-Mannich bases 6a-o, 7a-g and 11a-i. The newly synthesized N-Mannich bases 6a-o, 7a-g and 11a-i were tested for in vitro inhibitory activities against a panel of Gram-positive and Gram-negative bacteria and the yeast-like pathogenic fungus Candida albicans. The compounds 6j, 6l, 6m, 7a, 7b, 7c, 7d, 7f, 11a, 11b, 11c, 11d, 11e, 11f, 11h and 11i displayed moderate to good activity against the tested Gram-positive bacteria, while compounds 7c, 11c, 11d, 11f and 11h showed potent broad spectrum antibacterial activity. None of the newly synthesized compounds were proved to possess marked activity against C. albicans.
- El-Emam, Ali A.,Al-Tamimi, Abdul-Malek S.,Al-Omar, Mohamed A.,Alrashood, Khalid A.,Habib, Elsayed E.
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- Synthesis, antimicrobial, and anti-inflammatory activities of novel 5-(1-adamantyl)-4-arylideneamino-3-mercapto-1,2,4-triazoles and related derivatives
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The reaction of 5-(1-adamantyl)-4-amino-3-mercapto-1,2,4-triazole (5) with various aromatic aldehydes in ethanol or acetic acid yielded the corresponding 4arylideneamino derivatives 6a-v. Treatment of the 4-(2,6-difluoro- and dichlorobenzylideneamino) derivatives 6o and 6q with 1-substituted piperazines, and formaldehyde solution in ethanol afforded good yields of the corresponding 5-(1adamantyl)-4-(2,6-dihalobenzylideneamino-2-(4-substituted-1- piperazinylmethyl)-1,2,4triazoline-3-thiones 7a-p. 5-(1-Adamantyl)-4- arylideneamino-2-(4-ethoxycarbonyl-1piperidylmethyl)-1,2,4-triazoline-3-thiones 8a-n, were similarly prepared via the reaction of the corresponding arylideneamino derivative with ethyl 4-piperidinecarboxylate and formaldehyde solution in ethanol. Compounds 6a-v, 7a-p and 8a-n were tested for in vitro activities against a panel of Gram-positive and Gram-negative bacteria and the yeastlike pathogenic fungus Candida albicans. Several derivatives showed good or moderate activities, particularly against the tested Gram-positive bacteria. In addition, the in vivo anti-inflammatory activity of 21 compounds was determined using the carrageenan-induced paw oedema method in rats. Compounds 7d, 7g, 7i, 7j, 7l, 8c, 8e and 8l showed good or moderate dose-dependent activity in this area. Copyright
- Al-Omar, Mohamed A.,Al-Abdullah, Ebtehal S.,Shehata, Ihsan A.,Habib, Elsayed E.,Ibrahim, Tarek M.,El-Emam, Ali A.
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scheme or table
p. 2526 - 2550
(2010/08/05)
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- Reactions of adamantyl-substituted keto esters with hydrazine and phenylhydrazine
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Reactions of adamantyl-substituted keto and diketo carboxylic acid esters with hydrazine and phenylhydrazine were studied. Ethyl 3-(1-adamantyl)-2-(1- adamantylcarbonyl)-3-oxopropanoate reacted with hydrazine to give ethyl 3,5-di(1-adamantyl)-1H-pyrazole-4-carboxylate. Reactions of ethyl 2-(1-adamantylcarbonyl)-3-oxobutanoate and ethyl 4-(1-adamantyl)-3-oxo-2-(1- oxoethyl)butanoate with hydrazine and phenylhydrazine followed a complicated pattern and led to the formation of mixtures of the corresponding hydrazides and pyrazolones.
- Bormasheva,Nechaeva,Moiseev
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experimental part
p. 1760 - 1764
(2009/09/06)
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