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A series of 1,2,3-triazol-1-ylbenzenesulfonamide derivatives was designed, synthesized and their ability to inhibit several carbonic anhydrase isoforms was evaluated. The basis of our design is to hybridize the benzenesulfonamide moiety widely used as a zinc-binding group, a triazole ring as spacer with a tail of different substituted aryl moieties. The synthesis of these compounds was achieved using Cu(I)-mediated click chemistry between the azide containing the benzenesulfonamide pharmacophore and various aryl acetylenes or 1,6-heptadiyne through copper-catalyzed [3+2] cycloaddition reaction. The ability the new derivatives to inhibit four human carbonic anhydrase isoforms hCA I, II, IX, and XII was evaluated. All the compounds exhibited good potency and high selectivity towards isoforms hCA I and II more than isoforms hCA IX and XII, especially for the derivatives 3c and 3j that displayed K

Microtubules and the mitotic spindle have become an important target for cancer treatment due to their critical role in cell division. In this work, a novel series of benzofuran and indole derivatives were designed and synthesized, to be evaluated as tubulin polymerization inhibitors. 2-Acetylbenzofuran derivatives 1a,b and 3-acetylindole 1c were condensed with Wittig reagents 2a-d and Wittig-Horner reagents 3a-e to afford the respective 2-ethylidene derivatives 5a-j and 7a-e. Also, iminomethylene triphenylphosphine (2e) reacted with 1a,b to afford benzofuran-2-ylethylidene aniline derivatives 6a,b. In addition, compounds 1a,b reacted with trialkylphosphites 4a-c to give 1:1 adduct for which the Oxaphospholo[4,3-b]benzofuran-7-yl)diazene derivatives 8a-f, were assigned. The possible reactions mechanisms were discussed and structural reasoning for the new compounds were based upon spectroscopic data. Their antiproliferative activities against two cell lines namely, HepG2 and MCF7 cells were then evaluated. It was found that the benzofuran compounds 5b, 6a, and 8c exhibited the strongest antiproliferative activities against both cell lines compared to doxorubicin. By studying the mechanism of action, compound 6a showed good inhibition of tubulin polymerization which leads to mitotic spindle formation disruption, cell cycle arrest in the G2/M phase, and apoptosis of HepG2 cells. A conducted docking study confirmed the in vitro results indicating that compound 6a fitted properly at the colchicine binding site of tubulin. Based on these findings, compound 6a can be considered as a promising anticancer candidate that can be subjected for further development as a tubulin polymerization inhibitor for treating liver and breast cell carcinoma.

Our scope is synthesis a new poly fluorobenzamide oxime ester and study its structural, optical, and dielectric properties. Consequently, ((E)-2-((acryloyloxy)imino)-N-(4-fluorophenyl) acetamide) (AIFPA) was as-synthesized via a condensation reaction of (E)-N-(4-fluorophenyl)-2-(hydroxyimino) acetamide with acrylic acid to polymerize it via free radical polymerization (PAIFPA). over and above, the synthesized PAIFPA was inserted in more polymerization action with polystyrene sulfonate through the grafting process (PAIFPA-co-PSS). The chemical structures and morphology of AIFPA, PAIFPA, and PAIFPA-co-PSS were characterized by 1H NMR, FTIR, and XRD. The crystallinity index of PAIFPA, and PAIFPA-co-PSS was studied, affording that PAIFPA-co-PSS has the highest crystallinity. Moreover, The optical bandgap that obtained from absorbance analysis was encountered to be in the range of 2.6 eV to 3.5 eV. Ultimately, the dielectric properties of PAIFPA, and PAIFPA-co-PSS showed that electric conductivity values ranged from 6.12 × 10–8 to 7.11 × 10–7 S.cm−1, and 5.48 × 10–10 to 7.75 × 10–8 S.cm−1, respectively. It has a great deal of interest of PAIFPA-co-PSS which has wide band gap energy as short-wavelength light absorbers to be used in tandem polymer solar cells.

5-Amino-2,3-dihydrophthalazine-1,4-dione (Luminol 1) reacted with some organophosphorus reagents such as phosphonium ylides, trialkyl phosphites, and tris(dialkylamino)phosphines to afford the corresponding olefinic products 5a-e, alkoxy-, and dialkylamino derivatives of Luminol 6a-e. 4-Thioxo-3,4-dihydrophthalazin-1(2H)-one derivative 7 was synthesized from the reaction of Luminol (1) with thiating Lawesson and Japanese reagents. Structures of the synthesized compounds were clarified based on their elemental and spectroscopic analyses. The synthesized compounds were evaluated for their antimicrobial activity against some bacterial and fungal strains.

Series of novel sulfonamide-based 3-indolinones 3a-m and 4a-f were designed, synthesized and then their cytotoxic activity was evaluated against a panel of sixty cancer cell lines. This screening indicated that 4-(2-(5-fluoro-2-oxoindolin-3-ylidene)acetyl)phenyl benzenesulfonate (4f) possessed promising cytotoxicity against CCRF-CEM and SR leukemia cell lines with IC50 values 6.84 and 2.97 µM, respectively. Further investigation of the leukemic cytotoxicity of compound 4f was carried out by performing PDGFRα, VEGFR2, Aurora A/B and FLT3 enzyme assays and CCRF-CEM and SR cell cycle analysis. These investigations showed that compound 4f exhibited pronounced dual inhibition of both kinases PDGFRα and Aurora A with potency of 24.15 and 11.83 nM, respectively. The in vitro results were supported by molecular docking studies in order to explore its binding affinity and its key amino acids interactions. This work represents compound 4f as a promising anticancer agent against leukemia.

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.

A series of α-aminophosphonates (3a-3m) bearing the sulfisoxazole moiety was synthesized through one-pot Kabachnik-Fields reaction of sulfisoxazole, diethyl phosphite (DEP) and substituted aldehydes using bismuth (III) triflate [Bi(OTf)3] as a catalyst under microwave reaction conditions. The novel compounds are identified by their spectroscopic data and confirmed by X-ray diffraction studies of diethyl (4-chlorophenyl)(4-(N-(3,4-dimethylisoxazol-5-yl)sulfamoyl)phenylamino) methylphosphonate 3g. The antimicrobial properties of the synthesised agents were examined against a range of bacterial species and C. albicans yeast. Some of the synthesised agents, 3j, 3l and 3m, exhibit potent antimicrobial activities against the five pathogenic microorganisms used in the investigation. Compound 3m is the most promising agents among all the synthesized derivatives, showing a potent and broad-spectrum antibacterial activity. The MIC values are 94.2 and 205.7 µM for 3m and sulfisoxazole, respectively for S. typhi (about 2.1 times potency). The MIC values are 102.8 and 187.0 µM for 3m and sulfisoxazole, respectively for L. monocytogenes. The observed biological properties are explained and supported by QSAR models.

Iron-based catalysts were applied in cascade-type reactions for the synthesis of different carbonyl compounds. The reactions proceeded by a new iron-catalyzed cascade of alkynylation/hydration by using both the σ- and π-Lewis acid properties of iron salts. The alkynylation reactions of several endo and exocyclic acetoxylactams were achieved with three different catalysts including FeCl3 ⋅ 6H2 O, FeCl3 , and Fe(OTf)3 showing the efficiency of σ-Lewis acidity of iron (III) salts in catalyzing the alkynylation reaction. We also demonstrated that the reaction sequence could be shortened by the direct use of hydroxylactams, leading to an environmentally friendly protocol, avoiding the need to perform unnecessary lengthy steps. A combination of the hard/soft iron Lewis acid properties was then used to implement an unprecedented tandem intermolecular alkynylation/intramolecular hydration sequence allowing expedient access to a new carbonyl structures from trivial materials.

A substituted benzimidazole and benzindazole derivatives had been synthesized having antihypertensive activity through antagonizing the angiotensin II (Ang II) receptors. The in vivo antihypertensive activity of the compounds was done with acute renal hypertension model. Two compounds TG 1 and TG 3 were found to have antihypertensive activity comparable to Telmisartan which is a prototype for Angiotensin II receptor antagonists class of drugs.In an antihypertensive study the compounds TG 1, TG 2 and TG 3 had systolic blood pressures of 147.2 mm/Hg, 168.2 mm/Hg, and 126.3 mm/Hg, respectively. This systolic blood pressure was lower than the disease control vehicle-treated rodents, which had a systolic blood pressure of 167.2 mm/Hg. The diastolic blood pressure was 119.7 mm/Hg, 124.7 mm/Hg and 88.83 mm/Hg, respectively and that of the disease control vehicle-treated rodents was 122.3 mm/Hg. TG 3 had comparable decrease in the MABP to Telmisartan. These encouraging results make compound TG 3 effective anti-hypertensive drug candidate and worthy of further investigation.

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.

The reaction of 1,1-bis(diphenylphosphino)methane with substituted o-quinones afforded the novel 6-[bis(diphenylphosphoryl)methyl]-, and 6-bis(diphenyl phosphoryl)methylidene derivatives. Moreover, 1,1-bis(diphenylphosphino)methane reacts with 3,4,5,6-tetrabromo-o-benzoquinone to give only the new 6-[bis(diphenylphosphoryl)methyl] derivative. Mechanisms accounting for the formation of the new products are discussed. The antimicrobial activity of some of the newly synthesized compounds was also examined.

The reactions are reported of 4-(furan-3-ylcarbonyl)-1,5-diphenylpyrrolidine-2,3-dione with six classes of organophosphorus reagents: carboalkoxymethylene triphenylphosphoranes, triphenyl (phenylimino)-λ5-phosphane, trialkylphosphonoacetates, trialkylphosphites, tris (dialkylamino)phosphines, and Lawesson's reagent. Several of the products showed antitumour activity.

The reaction of 5(4H)-pyrazolone with phosphorus ylides afforded new triphenylphosphanylidene alkanone derivatives. Moreover, its benzylidene derivative reacted with Wittig–Horner reagents to give the corresponding dialkoxyphosphoryl, alkyl phosphonate, and heterocyclic products. Treatment of pyrazole-4-carbaldehyde with Wittig–Horner reagents and trialkyl phosphites gave the respective alkyl phosphonate adducts. Mechanisms accounting for the formation of the new products are discussed. The biological activity of some of the newly synthesized compounds was also examined.

The reaction of 1,2-bis(diphenylphosphino)ethane with substituted o-benzo-quinones afforded new bis(6-hydroxycyclohexa-2,4-dienone) derivatives. Treatment of the same reagent with o-naphthoquinone, phenanthrenequinone, and acenaphthenequinone gave the respective bis(diphenylphosphoryl)ethylidenes or diacenaphthylenone derivatives. On the other hand, p-quinones react with 1,2-bis(diphenylphosphino)methane to yield the corresponding 4-hydroxycyclohexa-2,5-dien-1-ones. Possible reaction mechanisms are considered and the structural assignments are based on compatible analytical and spectroscopic data.

The reaction of 5(4H)-oxazolones with tetraethyl methanediylbis(phosphonate) afforded new 1,1-bisphosphonate and 1,1-bisphosphonic acid derivatives. Moreover, 5(4H)-oxazolones reacted with Wittig reagents to give the corresponding heterocyclic products. Treatment of 5(4H)-oxazolones with trisdialkylaminophosphanes gave the corresponding N-(1-dialkylcarbamoyl)-2-phenylvinylbenzamides. Mechanisms accounting for the formation of the new products are discussed. The biological activity of the newly synthesized compounds was also examined.

4-Benzylidene-2-phenyl-5(4H)-oxazolones react with Wittig-Horner reagents in the presence of alcoholic sodium alkoxide to give novel dioxopyrrolidinephosphonates, diethyl [3-(benzoylamino)- 1-cyano-2-oxo-4-phenylbut-3-en-1-yl]phosphonate and phosphonoalkenoate derivatives. Both the phosphonate adducts and the ester products were also isolated from the reaction of oxazolones with triethyl phosphonoacetate using alcoholic sodium ethoxide and/or sodium hydride as a base. Possible reaction mechanisms are considered, and the structural assignments are based on analytical and spectroscopic results. The biological evaluation of the new compounds is reported.

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.

3-Methyl-2-benzothiazolinone hydrazone condensed with some selected aldehydes to give the corresponding Schiff bases. Cyclizing the obtained Schiff base derivatives with thioglycolic acid afforded the respective thiazolylideneaminothiazolidenones. Condensation of 3-methyl-2-benzothiazolinone hydrazone with ethyl cyanoacetate yielded a mixture of the bishydrazine and the cyanoacetohydrazide derivatives. Meanwhile, its condensation with ethyl acetoacetate produced a mixture of the monoketone and the β-diketone derivatives. Besides, the reaction of the starting hydrazone with malononitrile afforded a mixture of the cyanomethylylidene and cyanomethyl hydrazone derivatives beside the bishydrazine derivative. Elementary and spectroscopic measurements were in good accord with the structures postulated for the new compounds. The antitumor activities of certain selected new compounds were screened, in vitro, against a panel of four (liver, HepG2; breast, MCF-7; lung, A549; and colon; HCT116) human solid tumor cell lines. The cells that showed better activity were HepG2 and MCF-7. Structure-activity relationship (SAR) was also discussed.

The reactions of 2-aryl-5(4H)-oxazolones with phosphonates, phosphates, and tris(alkylamino)phosphines are studied and the underlying different reaction mechanisms are discussed.