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6-[2-(Furan-2-yl)ethyl]-3-sulfanylidene-3,4-dihydro-1,2,4-triazin-5(2H)-one (1) reacted with chloroacetone to give S-acetonyl derivative which cyclized in ethanol under reflux to afford 6-[2-(furan-2-yl)-ethyl]-3-methyl-7H-[1,3]thiazolo[3,2-b][1,2,4]triazin-7-one. 2,4-Bis(furan-2-carbonyl)-6-[2-(furan-2-yl)-ethyl]-3-sulfanylidene-3,4-dihydro-1,2,4-triazin-5(2H)-one and 3-amino-6-[2-(furan-2-yl)ethyl]-2-{[6-(2-(furan-2-yl)ethyl)-5-oxo-2,5-dihydro-1,2,4-triazin-3-yl]sulfanyl}-3-methyl-7H-[1,3]thiazolo[3,2-b][1,2,4]-triazin-7-one were prepared by reaction of 1 with furoyl chloride and dibromoacetonitrile, respectively. Compound 1 also reacted with formaldehyde and with formaldehyde and benzylamine to give 2-hydroxymethyl and 2-(benzylaminomethyl) derivatives. The alkylation of 1 with methyl iodide, followed by treatment with hydrazine hydrate, afforded 6-[2-(furan-2-yl)ethyl]-2-hydrazinyl-1,2,4-triazin-5(2H)-one. Reactions of the latter with aromatic aldehydes and formic acid furnished 3-aryl- and 3-unsubstituted 6-[2-(furan-2-yl)ethyl][1,2,4]tri-azolo[4,3-b][1,2,4]triazin-7(1H)-ones, respectively, and triacetyl and tetrabromophthalazinyl derivatives were obtained by reacting hydrazinyltriazinone with acetic anhydride and tetrabromophthalic anhydride. The newly synthesized compounds were evaluated for their antimicrobial activity against some bacterial and fungal strains.

A green approach for ethylene carbonate ring opening polymerization was proposed via an interaction between ethylene carbonate and 5-azido-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde (azidopyrazole) in presence of FeCl3 anhydrous as initiator. Despite the high thermodynamic stability of ethylene carbonate, reducing consumption of heat and time has been obtained. The effect of the molar ratio of azidopyrazole to ethylene carbonate has been studied and the resulted products were characterized.

Novel synthetic route for phosphanylidene-benzothiophenethione, benzothiaphosphinine-4-thione, triphenylphosphoranylidenecyclobutane and benzodithiolylidenephosphonate derivatives has been proposed...

A new series of coupled benzofuran derivatives that contain the trifluoromethyl group and pyrazole moiety is synthesized for evaluation of their anti-inflammatory and analgesic activities. Their synthesis proceeds via cyclocondensation of 2-hydroxy-4-(trifluoromethyl)benzaldehyde with chloroacetone with formation of 2-acetylbenzofuran, which upon treatment with different aldehydes via the Claisen-Schmidt condensation gives the corresponding chalcones. Cyclization of chalcones with hydrazine hydrate leads to pyrazoline derivatives, that exhibit significant anti-inflammatory and analgesic activities. Docking modelling of selected active compounds are correlated well with their anti-inflammatory tests data.

α-aminophosphonate oxadiazoles (5a-m) were prepared in high yields by reacting of 1,3,4-oxadiazole acetohydrazide (3) with appropriate aldehydes and diethyl phosphite under Kabachnik-Fields conditions using Iron triflate as a catalyst. The reaction conditions were optimized using D-optimal experimental design. Possible reaction mechanisms were considered, and structures of the new products were based upon compatible elementary and spectroscopic evidence. In vitro antitumor activities of these compounds were evaluated against human cancer cell lines of colon (HCT116), breast (MCF7) and liver (HepG2) and compared with anticancer drug, Doxorubicin, employing standard MTT assay. Compounds 5i and 5l demonstrated good antiproliferative activities against HCT116 tumor cells comparable to doxorubicin with low cytotoxicity towards normal fetal colon cell (FHC). Additionally, their capacity to activate apoptosis cascade was studied in HCT116 cell line by investigating the activation of proteolytic caspases cascade, the levels of Cytochrome C, Bax and Bcl-2. Active caspase-3 level was enhanced by 6-8-folds in HCT116 cell line when stimulated with compounds 5i and 5l compared to the control. The level of Caspases 8 & 9 was also increased signifying that intrinsic and extrinsic pathways are both activated. They also induced Bax and down regulated Bcl-2 protein level in addition to over-expressing Cytochrome C level in HCT116 cell line. Also, HCT116 cell cycle was mainly arrested at the Pre-G1 and G2/M phases when treated with compounds 5i and 5l.

The reactions of bis(diphenylphosphino)alkanes with benzophenone, bis(piperidinocarbonyl)diazene, isatin, and quinoxaline1,4-di- N-oxide have been studied and the products characterised by elemental analysis and spectroscopic measurements.

Phthalocyanines have interesting optoelectronic properties but typically suffer from aggregation in aqueous solution, which can limit their applicability, especially in photodynamic therapy. In this study, indium(III) phthalocyanine peripherally substituted with eight triazolyl-containing phenoxy groups (InOAc) and its water-soluble analogue (Q-InOAc) were synthesised and structurally characterised. Heavy metal effects, exerted by the central indium ion, on the photosensitising and photophysical properties (singlet oxygen quantum yield, singlet state lifetime and quantum yield, and triplet state lifetime) were investigated in both DMF and D2O. Highly efficient generation of the triplet excited state (T1), induced by the incorporation of a large atom, enhanced singlet oxygen formation, as revealed by both chemical and physical methods. Correspondingly, the singlet oxygen quantum yield (ΦΔ) of Q-InOAc was 0.603 in DMF and 0.433 in D2O. These values are higher than those previously reported for the corresponding metal-free, Mg-based, and Zn-based water-soluble phthalocyanines (HH, Mg, and Zn). Consequently, Q-InOAc is expected to be an excellent photosensitiser for photodynamic therapy.

Phosphazine and phosphazide derivatives are described herein as a new class of selective and potent acetylcholinesterase (AChE) inhibitors and β-amyloid aggregation inhibitors. Phosphazines (5–7) were synthesized smoothly via a redox-condensation reaction of 1,2-bis(diphenylphosphino)ethane with different amines derivatives in the presence of dialkyl azodicarboxylate (Staudinger reaction) while phosphazides (8) via electrophilic attack of azido derivatives. Structures of the synthesized compounds were justified on the basis of compatible elementary and spectroscopic analyses. All the compounds were evaluated for their acetylcholinesterase inhibitory activity. The most three potent compounds (5b-c and 8b) showing AChE IC50 values (29.85–34.96 nM) comparable to that of donepezil (34.42 nM) were subjected to further investigation by testing their butyrylcholinesterase, MMP-2 and self-induced Aβ aggregation inhibition activity. Especially, the coumarin phosphazide derivative (8b) presented the best AChE inhibition selectivity index (IC50 = 34.96 nM, AChE/BuChE; 3.81) together with good inhibition ability against MMP-2 (IC50 = 441.33 nM) and self-induced Aβ1-42 aggregation (IC50 = 337.77 nM). In addition, the inhibition of metal-induced Aβ aggregation by 8b was confirmed by thioflavine T fluorescence. The most potent effect of 8b was observed on the Zn2+-induced Aβ42 aggregation. Kinetic study of compound 8b suggested it to be a competitive AChE inhibitor. Also, it specifically chelates metal and is predicted to be permeable to BBB. It also possesses low toxicity on SH-SY5Y neuroblastoma cells with a safety index of 15.37. In addition, it was demonstrated that compound 8b can improve the cognitive impairment of scopolamine-induced model in mice with % alternations and transfer latency time comparable to that of donepezil. Also, a docking study was carried out and it was in accordance with the in vitro results. These promising in vitro and in vivo findings highlight compound 8b as a possible drug candidate in searching for new multifunctional AD drugs.

New 2-(thiophen-2-yl)-1H-indole derivatives bearing hydrophobic substituents at the 3-position were designed, synthesized and evaluated for their inhibition of HIV-1 reverse transcriptase (RT) enzyme. Dialkylphosphites (2a-c) or trialkylphosphites (3a-c) were reacted with 2-(thiophen-2-yl)-1H-indole-3-carbaldehyde (1) yielding the corresponding α-hydroxyphosphonate adducts (7a-7c). The reaction of compound 1 with the ylidenetriphenylphosphoranes (4a-4c) proceeds via Wittig mechanism giving the corresponding ethylenes (E, 8a-c). Compounds 8b,c were equally obtained upon reacting aldehyde 1 with the appropriate dialkylphosphonates 5a,b under the Horner-Wittig reaction conditions. On the other hand, the reaction of aldehyde 1 with diethyl cyanomethylene phosphonate (5c) yielded a mixture of the E-ethylene 10 and the cyanovinyl phosphonate 11. The thioaldehyde 12 was obtained upon refluxing aldehyde 1 with the Lawesson’s reagent (LR, 6a) or with the Japanese reagent (JR, 6b) in dry toluene. Upon evaluation of HIV-1 Reverse Transcriptase enzyme inhibition, compound 8b (IC50 = 2.93 nM) exhibited the superior HIV-1 RT inhibition and its potency was about 3-folds that of Efavirenz (IC50 = 6.03 nM). Also, compounds 9a (IC50 = 4.09 nM) and 12 (IC50 = 3.54 nM) showed significantly higher inhibition potency. Moreover, compounds 7b (IC50 = 7.48 nM), and 8a (IC50 = 4.55 nM) showed potency not significantly different from that of Efavirenz. Molecular docking experiments on these potent compounds was in accordance with the in vitro data and confirmed binding of these compounds to the enzyme through ring-stacking and hydrogen bond interactions. According to these results, the new molecules would serve as potent HIV-1 NNRTIs inhibitors.

Reactions of 3-amino-4-aminoximidofurazan (AAOF) with Wittig–Horner reagents, trialkylphosphites, trisdialkylaminophosphines as well as the thiating Lawesson and Japanese reagents were studied. Elemental analysis and spectroscopic measurements were in good accord with the structures postulated for the new products. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of five (liver; HepG2; breast; MCF-7; lung; A549; colon; HCT116; and prostate PC3) human solid tumor cell lines.

An asymmetrical, push&ndash, pull phthalocyanine bearing bulky tert-butylcarbazolyl moieties as electron donor and carboxylic acid as anchoring group was synthetized and tested as a photosensitizer in dye-sensitized solar cells (DSSC). The new photosensitizer was characterized by 1H and 13C NMR, UV&ndash, Vis and mass spectrometry. The bulky tert-butylcarbazolyl moieties avoid the aggregation of the phthalocyanine dye. DFT studies indicate that the HOMO is delocalized throughout the -electron system of the substituted phthalocyanine and the LUMO is located on the core of the molecule with a sizable electron density distribution on carboxyl groups. The new dye has been used as a photosensitizer in transparent and opaque dye-sensitized solar cells, which exhibit poor efficiencies related to a low Jsc.