Sugar Hydrazones Research Articles

Design, Synthesis, and Docking Simulation of 1,3,4-Thiadiazolyl-Isoindole Thioglycosides and Hydrazinyl Sugar Analogs as Potential Anticancer Agents Targeting EGFR Kinase

The development of efficient strategies for overcoming cancer remains a standing objective in medicinal chemistry. Design and synthesis of new potent compounds contribute efficiently to chemotherapy strategy since molecular hybridization was found an efficient strategy for designing new candidates of possible potent anticancer activities. Isoindole and 1,3,4-thiadiazole as well as glycosyl structures are known in literature with their broad-spectrum activities, the most important of which is anticancer activity. In this study, novel hybrid compounds incorporating more than motif were synthesized. A multistep synthetic pathway starting from the simple 2-amino-1,3,4-thiadiazole-2-thiol and the commercially available phthalic anhydride was applied for the preparation of the hybrid heterocyclic system. Glycosylation by acetylated glycosyl bromide and reaction with a series of monosaccharides afforded the corresponding glycosylthio-1,3,4-thiadiazole based isoindole products and the hydrazinyl-sugar derivatives, respectively. 1,3,4-Thiadiazolyl-isoindolyl-sugar compounds and related arylidenes were prepared. The cytotoxicity activity was investigated against human cancerous MCF-7, PC-3, A-549 and normal BJ-1 cells. The iodobutylthio-1,3,4-thiadiazolyl derivative exhibited the most potent activity against A-549 cell. The hybrid thiadiazolyl-sugar-based isoindole structure with the hydrazinyl-per-O-acetylated-D-galactose moiety exhibited the most potent activity against MCF-7 cell. Docking into epidermal growth factor (EGFR) revealed that the later bioactive compounds presented promising energy scores showing good affinity and various binding interactions into EGFR active site. In addition, Molecular dynamics (MD) simulation was performed to investigate the stability of the EGFR enzyme’s binding domain applying a 100 ns simulation analysis on the docked complex of EGFR with the potent compound 10 which showed that the sugar hydrazone 10 remained in the EGFR binding cavity over the 100 ns simulation with different orientations.

Synthesis, Antioxidant, and Anticancer Studies of New 1,3,4‐Oxadiazole Derivatives Linked to Benzoquinoline

AbstractA series of some new 1,3,4‐oxadiazole derivatives was synthesized. Hydrazide derivative 4 was reacted with some sugar aldehydes to give the corresponding sugar hydrazones 5 a–c. Acetylation of 5 a–c with acetic anhydride in pyridine, managed the per‐O‐acetyl derivatives 6 a–c while refluxing in acetic anhydride gave the corresponding 1,3,4‐oxadiazolines 7 a–c. On the other hand, 1,3,4‐oxadiazoles 8 a,b, 9, 10, 12, 14, and 15 were synthesized via the reaction of 4 with different reagents including p‐chlorobenzoic acid, nicotinic acid, methyl iodide, morpholine, phenyl isothiocyanate, potassium iodide, chloroacetyl chloride, and phosphorus oxychloride, respectively. The new compounds were assessed for their anticancer and antioxidant activities. Compounds 8 a,b, 10, and 12–15 displayed the most antioxidant activity. In addition, compounds 8 a, 8 b, and 13 showed strong cytotoxic activity.

Synthesis, conformational analysis and antimicrobial activity of 10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indole acyclo C-nucleoside analogs

Condensation of 5-benzyl-3-hydrazino-1,2,4-triazino[5,6-b]indole with various sugar aldoses or ketoses gave the corresponding sugar hydrazones as single geometrical isomer or exist in E/Z tautomeric isomers. The hydrazones underwent heterocyclization with Fe(Ш)Cl3 to give the N2-adduct acyclo C-nucleosides: 3-(alditol-1yl)-10-benzyl-1,2,4-triazolo[4,3-b]1,2,4-triazino[5,6-b]indoles rather than the N4-adduct: 10-(alditol-1-yl)-3-benzyl-1,2,4-triazolo[3,4-c]1,2,4-triazino[5,6-b] indoles on the basis of chemical and UV spectral proofs. Conformational analysis of their polyacetates were studied. The new acyclo C-nucleosides were evaluated for antimicrobial activity.

Chiral Discrimination of Monosaccharides Derivatized with 2-Fluorophenyl Hydrazine Using 19F NMR Spectroscopy.

Chiral discrimination of monosaccharides holds significant importance, especially given the growing interest of the pharmaceutical industry in their utilization. However, the majority of existing methods has predominantly centered around chromatographic techniques. In this study, we introduce a 19F NMR-based comprehensive approach for chiral analysis specifically tailored for 15 pairs of aldoses. This technique involves employing sugar hydrazones containing fluorine in combination with chiral octahedral gallium and scandium complexes. By utilizing highly sensitive 19F NMR spectroscopy, the fluorine label in the sugar hydrazone enables accurate differentiation between d and l enantiomers. The efficiency of the newly developed method was demonstrated through its successful application in both quantitative and qualitative analyses of mixtures containing various monosaccharides.

Synthesis, characterization and photo-physical properties of sugar hydrazones having indole and 1,3,4-oxadiazole moiety

Oxadiazole-indole hybrids are interesting molecules and show excellent photophysical properties emitting light in the visible region. In the present study, the photophysical property of a series of indole-oxadiazole hydrazides 8a-f and their sugar-hydrazones 9a-f were investigated. All studied molecules were characterized using ATR-IR, 1H NMR, 13C NMR, and mass spectrometry. The optical properties of compounds were studied using UV–visible and photoluminescence spectroscopy. Density functional theory (DFT) calculations were done to study the structural properties of hydrazides and their sugar hydrazones. Emission spectra of all compounds showed bands around 385–437 nm with quantum yields ranging from 10.89 to 18.65%. Overall, the obtained results indicate that these compounds could be used as optoelectronic materials in the future.

Synthesis and Cytotoxic Activity of New N-(Arylglycyl)succinohydrazide and their Sugar hydrazone derivatives

Synthesis and Cytotoxic Activity of New N-(Arylglycyl)succinohydrazide and their Sugar hydrazone derivatives

Anticancer activity, spectroscopic and molecular docking of some new synthesized sugar hydrazones, Arylidene and α-Aminophosphonate derivatives

In this work, we design and then synthesis of new derivatives of nucleosides, oxadiazoline derivatives containing acetylated sugars and α-aminophosphonate derivatives. The synthesized compounds have been elucidated by different spectroscopic analysis, such as, elemental analysis, 13 C NMR, infrared (IR) and 1 H NMR. The compounds previously synthesized were purified and then tested against breast cancer cells (MCF-7). The results showed that the compounds 5d , 6b , 7a and 9h showed moderate to very high activity against breast cancer, with incidence rates of 78.45%, 84.60%, 93.45% and 95.78%, respectively. The reference ratio of 5-fluorouracil was inhibitory of 96.02%. The binding potential of synthesized compounds against thymidylate synthase (TS) and Cathepsin B (CB) has been investigated and the compounds 7a and 9h exhibits highly binding with thymidylate synthase (TS) and Cathepsin B (CB).

Synthesis and Cytotoxic Activity of New Substituted Pyrazolo[3,4-b]pyridine Derivatives and Their Acyclic Nucleoside Analogs

As an important strategy, including incorporation of more than active core in one molecule, for finding potent candidates against cancer cells, a number of functionalized pyrazolopyridin derivatives linked to oxadiazole, dioxolane, acyclic sugar and fluorene ring systems, were synthesized through heterocyclization reactions. The derived sugar hydrazone and the corresponding acyclic C-nucleoside analog in addition to acyclic N-nucleoside were also prepared. The behavior of the afforded compounds as possible cytotoxic agents against human HTC116 and MCF7 cancer cells was investigated and the results showed that compounds 11-13 showed the highest activities against the two cancer cells. Other compounds revealed a type of selectivity toward one cancer cell while the activity was relatively lost against the other cancer cell line.

Synthesis and Anticancer Activity of New Pyridine-Thiophene and Pyridine-Furan Hybrid Compounds, Their Sugar Hydrazone, and Glycosyl Derivatives

New sugar hydrazones and their derived oxadiazolyl acyclic nucleoside analogs in addition to the derived thioglycosides incorporating pyridine, furan or thiophene have been synthesized via a multi-component reaction (MCR). The acetylated derivatives of hydrazones and the derived deprotected thioglycosides of the prepared acetylated analogs have been also synthesized. Anticancer activity of the products has been tested against adenocarcinomic human alveolar basal epithelial (A549), human prostatic adenocarcinoma (PC3) and human colorectal carcinoma (HCT116) cell lines in addition to their effect on human normal retinal pigmented epithelial cell line (RPE1) using the MTT assay. Three products: acid hydrazide, sugar hydrazine and glycoside are characterized by high activity against three cancer cell lines.

Synthesis of new uracil derivatives and their sugar hydrazones with potent antimicrobial, antioxidant and anticancer activities

6-(4-Chloro-3-nitrophenyl)-4-oxo-2-thioxo-1,2,3,4-tetrahydropyrimidine-5-carbonitrile (4) was prepared and was reacted with ethyl chloroacetate, hydrazine hydrate, 4-chloroaniline, formaldehyde, acetic anhydride, formic acid, carbon disulfide, 4-cyanobenzaldehyde, triethyl orthoformate, D-sugars, 4-aminoacetophenone, benzoyl choride and cyclohexanone to afford a series of new uracil derivatives (5–18). Examination of some of the prepared compounds for their antimicrobial, antioxidant and anticancer activities was conducted. Among the tested samples, compound 17 was the most active substance against the gram-positive bacteria and was more potent than the reference drug Cefoperazone. Moreover, the antibacterial activity of 17 was higher against gram-negative bacteria. Compounds 6 and 13 reached a higher scavenging ability toward DPPH radicals and are better candidates for antioxidant activity. Also, compounds 6 and 13 had no significant anticancer activity toward liver cancer (Hep G2) and breast cancer (MCF-7) cell lines.

Synthesis and Cytotoxic Activity of New Thiazolopyrimidine Sugar Hydrazones and Their Derived Acyclic Nucleoside Analogues.

New thienyl- or chlorophenyl-substituted thiazolopyrimidine derivatives and their derived sugar hydrazones incorporating acyclic d-galactosyl or d-xylosyl sugar moieties in addition to their per-O-acetylated derivatives were synthesized. Heterocyclization of the formed sugar hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the cyclization process. The cytotoxic activity of the synthesized compounds was studied against human breast cancer MCF7 and MDA-MB-231 cell lines as well as human colorectal cancer HCT 116 and Caco-2 cell lines. High activities were revealed by compounds 1, 8, 10, 11, and 13 against Caco-2 and MCF7 cells in addition to moderate activities exhibited by other compounds against HCT116 or MDA-MB-231 cells.

Synthesis, characterization, anticancer activity, and molecular docking of some new sugar hydrazone and arylidene derivatives

New sugar hydrazone moieties, their oxadiazoline derivatives, and arylidene analogues were prepared and chemically elucidated using spectroscopic analysis, such as nuclear magnetic resonance, for hydrogen 1HNMR, carbon 13CNMR, elemental analysis, and Infrared (IR). The prepared compounds were purified and tested against breast cancer cells (MCF-7). Compounds 4c, 4d, 6b, and 6d exhibited moderate to very high anti-breast cancer activity, with a percentage of inhibition of 96.19%, 93.08%, 74.33%, and 86.05% respectively; the reference 5-fluorouracil had an inhibitory percentage of 96.02%.

Synthesis and Antiviral Activity of Novel Thieno[2,3-d]pyrimidine Hydrazones and Their C-Nucleosides

A hydrazinylthienopyrimidine derivative reacted with a number of monosaccharides in the presence of a catalytic amount of acetic acid giving the corresponding sugar hydrazones, that undergo oxidative cyclization under the action of ferric chloride with formation of triazolo derivatives. Structures of the products have been elucidated from IR, 1H, and 13C NMR data. Antiviral activity of the newly synthesized compounds is tested against influenza virus H5N1.

Synthesis and Anticancer Activity of New ((Furan-2-yl)-1,3,4-thiadiazolyl)-1,3,4-oxadiazole Acyclic Sugar Derivatives.

New sugar hydrazones incorporating furan and/or 1,3,4-thiadiazole ring systems were synthesized by reaction of the corresponding hydrazide with different aldose sugars. Heterocyclization of the formed hydrazones afforded the derived acyclic nucleoside analogues possessing the 1,3,4-oxadiazoline as modified nucleobase via acetylation followed by the heterocyclization process. The anticancer activity of the synthesized compounds was studied against human liver carcinoma cell (HepG-2) and at human normal retina pigmented epithelium cells (RPE-1). High activities were revealed by compounds 3, 12 and 14 with IC50 values near to that of the reference drug doxorubicin.

Design, Synthesis of New Pyridine and Pyrimidine Sugar Compounds as Antagonists Targeting the ERα via Structure-Based Virtual Screening.

New aryl substituted cyclohepta[b]pyridine and cyclohepta[d]pyrimidine derivatives were synthesized. The sugar hydrazones of the synthesized pyridine and pyrimidine compounds were also prepared. In addition, the 1,3,4-oxadiazolyl acyclic C-nucleoside analogs of the pyridine system were prepared. The hemolytic, prebiotic, anticancer and antimicrobial activities of some of the synthesized compounds were also studied. Compounds 10 and 12 showed high activity against MCF-7, HEPG-2 and HCT-116 cell lines with IC50 at range 3.56-8.55 µg/mL. In addition, the synthesized condensed thiopyrimidine derivative 10 exhibited more potent bactericidal activity while compound 7 demonstrated potent antifungal activity against Aspergillus niger. Furthermore, the synthetic compounds of the pyrimidine base promoted the growth of lactic acid bacteria. The predicted binding patterns of three of the prepared derivatives as possible antagonists against ERα were investigated which showed good binding patterns.

Synthesis of New 3,7,9-Trisubstituted Pyrazolo[4,3-e][1,2,4]Triazolo[4,3-c] Pyrimidines Acyclo C-Nucleosides via Oxidative Cyclisation

Condensation of 4-hydrazino-1,3-diphenylpyrazolo[3,4-d]-pyrimidine with the aldohexoses, namely, D-glucose, D-galactose, D-mannose and the aldopentoses, D-arabinose, D-xylose and D-ribose, by heating in an aqueous ethanol in the presence of a catalytic amount of HCl, gave the respective aldehydo-sugar hydrazones. Oxidative cyclisation of such hydrazones by stirring with iron(III) chloride in ethanol at room temperature afforded the expected acyclo C-nucleosides 3-substituted-7,9-diphenylpyrazolo[4,3-e][1,2,4]triazolo[4,3-c]-pyrimidines. The structures of the cyclised sugar hydrazones were confirmed by their elemental analyses and spectral data.

Synthesis and Anti-H5N1 Activity of Substituted Pyridine Glycosides and (Oxadiazolyl)oxymethylpyridine Acyclic C-Nucleoside Analogues

New aryl- and heteroaryl-substituted pyridinyl sugar hydrazones and their derivatives, 1,3,4-oxadiazole acyclic C-nucleosides, were synthesized. Novel O-glycoside derivatives of the substituted pyridines were prepared. The antiviral activity against avian influenza H5N1 virus was studied and compounds 5a, 9a, and 14 demonstrated high inhibition activity.

Preparation of New Oxadiazole Acyclic Nucleoside and Thioglycoside Analogs Containing Chromene Moiety with Antimicrobial Evaluation

New sugar hydrazones linked to chroman ring system and their derived oxadiazole acyclic nucleoside analogs were synthesized from the substituted ethyl ester oxime derivative. The 2-sustituted 1,3,4-oxadiazole-5-thione prepared from acid hydrazide was glycosylated to afford the corresponding thioglycosides, not the N-linked glycosides. The novel compounds were evaluated for their antimicrobial activity and showed different degrees of activities.

Synthesis and anticancer activity of new [(Indolyl)pyrazolyl]-1,3,4-oxadiazole thioglycosides and acyclic nucleoside analogs

ABSTRACTNew [(Indolyl)pyrazolyl]-1,3,4-oxadiazole compounds and their derived thioglycosides as well as the corresponding sugar hydrazones were synthesized. The acyclo C-nucleoside analogs of the oxadiazoline base system were also prepared by reaction of acid hydrazides with aldehydo sugars followed by one pot process encompassing acetylation and cyclization of the synthesized hydrazones. The anticancer activity of the newly synthesized compounds was studied against colorectal carcinoma (HCT116), breast adenocarcinoma (MCF7) and prostate cancer (PC3) human tumor cell lines and a number of compounds showed moderate to high activities.

Synthesis of some novel 2-thioxoimidazolidin-4-one substituted glycosyl hydrazone derivatives

A series of novel 2-thioxoimidazolidine glycosides were prepared via reaction of the key intermediate 2-(benzylsulfanyl)-5-[4-(3-hydroxypropoxy)-3-(methoxybenzylidene)]-3-phenyl-1H-imidazol-4-one with different sugar aldose or sugar hydrazones to give the corresponding glycosides. The newly synthesized compounds were confirmed by physical and spectral data.