Eman M. H. Abbas

Hydrazonoyl Halides as Precursors for New Fused Heterocycles of 5α-Reductase Inhibitors

A new series of benzo[6,7]cyclohepta[1,2‐d]triazolo[4,3‐a]pyrimidines 8a–l was synthesized via reaction of heterocyclic thione 4 or its methyl derivatives 10 with hydrazonoyl halides 5a–l. Also, reaction of compound 4 with a mixture of chloroacetic acid and aromatic aldehyde derivatives gave benzo[6,7]cyclohepta[1,2‐d]thiazolo[3,2‐a]pyrimidin‐3‐ones 12–14. The microanalyses and spectral data of the synthesized compounds are in full agreement with their molecular structure. All the newly synthesized products were screened against 5α‐reductase and showed activities with good ED50 for all compounds.

Synthesis of 2-Phenylazonaphtho[1,8-ef][1,4]diazepines and 9-(3-Arylhydrazono)pyrrolo[1,2-a]perimidines as Antitumor Agents

Two series of naphtho[1,8-ef][1,4]diazepines and pyrrolo[1,2-a]perimidines were prepared starting from 1,8-diaminonaphthalene and hydrazonoyl chlorides. The structures of the products were determined on the basis of their spectral data and elemental analyses. The mechanism of formation of such products was also discussed. The prepared compounds were screened for their antitumor activity against three cell lines, namely, MCF-7, TK-10 and UACC-62, and some derivatives showed promising activity.

Synthesis and antimicrobial evaluation of novel 1,3-thiazoles and unsymmetrical azines

Abstract1,3-Thiazol derivatives have been synthesized via reaction of 1-(1-(5,6-dimethoxy-2-oxobenzo[d]thiazol-3(2H)-yl)propan-2-ylidene)-4-substituted thiosemicarbazide with different halides, namely, ethyl bromoacetate, ethyl-2-bromopropionate, phenacyl bromide, p-bromophenacyl bromide and/or substituted hydrazonoyl halides. The new compounds were evaluated as antimicrobial agents.

Synthesis, anti-inflammatory and antinociceptive activity of some novel benzothiazole derivatives

A new series of derivatives bearing benzothiazol-2-one or benzothiazole ring system conjugated to other different heterocycles were prepared using 5,6-dimethoxy-3-benzothiazol-2(3H)-one (1) as a starting material. The structures of the newly synthesized products have been established based on analytical and spectral data. In addition, the anti-inflammatory and antinociceptive activities of some of the products were evaluated. Our data showed that many derivatives have promising activities as anti-inflammatory and antinocicepative agents.

Hydrazonoyl halides as precursors for synthesis of novel bioactive thiazole and formazan derivatives

A new series of substituted 4-methyl-5-(arylazo)-2-[N‘-(6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene)-hydrazino]-thiazoles and 5-(arylhydrazono)-2-[N‘-(6,7,8,9-tetrahydro-benzocyclohepten-5-ylidene)-hydrazino]-thiazol-4-one were prepared by reaction of hydrazonoyl chlorides with a thiosemicarbazone derivative. The tautomeric structures of the products were studied using electronic absorption and NMR spectroscopy. The site-selectivities of the reactions of hydrazonoyl halides with benzocyclohepten-5-one hydrazone were also investigated. In addition, the antimicrobial activity of some of the products was evaluated. Many derivatives have promising activities against antibacterial and antifungal species.

Triazolopyrimidines and Thiazolopyrimidines: Synthesis, Anti-HSV-1, Cytotoxicity and Mechanism of Action

BACKGROUND Several commercial drugs utilized in the treatment of HSV containing pyrimidine moiety. Because of the ineffectiveness of virus drugs due to the resistance of the patients immune system, there is a pressing need to prepare new compounds that are effective in the treatment of various viruses. RESULTS Merged pyrimidine derivatives were designed by one pot synthesis of pyrimidinethione derivative with halogenated compounds. The structure of all prepared compounds was characterized by their spectroscopic data and also, their ability to inhibit the in vitro replication of HSV-1 was estimated. Amongst the tested compounds 2-acetyl-3-methyl-5-(p-tolyl)indeno[1,2-d]thiazolo[3,2- a]pyrimidin-6(5H)-one (9b) and ethyl 3-methyl-6-oxo-5-(p-tolyl)-5,6-dihydroindeno[1,2-d]thiazolo- [3,2-a]pyrimidine-2-carboxylate (9c), caused viral inhibition over 90%. Furthermore, the selectivity indices of the tested compounds are high and have weak cytotoxicity (all samples were checked, not chosen on cytotoxicity basis, we only utilize secure concentrations of every compound). CONCLUSION We succeeded in this context to synthesize a new series of potent fused pyrimidine derivatives as anti-HSV-1.

ZnO Nanoparticles catalyst in Synthesis of Bioactive Fused Pyrimidines as Anti-breast Cancer Agents Targeting VEGFR-2.

BACKGROUND Pyrimidines emerged as a remarkable class of heterocyclic compounds that have reinforced the pharmaceutical chemistry with various bioactive antitumor agents. Moreover, pyrimidine scaffold displayed VEGFR-2 inhibitory activity. Also, nano-sized catalysts are used in organic reactions in order to speed up the catalytic process. OBJECTIVE We were interested herein to synthesize a new series of fused pyrimidines using ZnO(NPs) to investigate their antitumor efficiency against breast MCF7 cancer and their VEGFR- 2 inhibition properties. METHOD A simple and efficient method for the synthesis of fused pyrimidines was developed using zinc oxide nanoparticles ZnO(NPs) in refluxing ethanol. RESULTS The proposed structures of all new fused pyrimidines are in agreement with their spectral data. Antitumor evaluation of newly fused pyrimidine derivatives against breast MCF-7 cancer was performed. It was apparent that the 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a (IC50 = 9.12±1.16 µg/ml), 9c (IC50 = 9.10±1.07 µg/ml) and 9d (IC50 = 9.60±1.22 µg/ml) exhibited equipotent antitumor activity as Tamoxifen (IC50 = 9.11±0.90 µg/ml). Also, the inhibitory activity of the novel fused pyrimidine derivatives on VEGFR-2 as well as Tamoxifen was determined using breast cancer cell line MCF-7. The data was obvious that 2-phenylpyrazolo[1,5-a]pyrimidine derivatives 9a, 9c and 9d exhibited noticeable VEGFR-2 inhibitory effect with % inhibition ranging from 80-84 % versus Tamoxifen 93.5%. CONCLUSION We succeeded in this context to synthesize new fused pyrimidines using ZnO(NPs) as anti-breast cancer agents targeting VEGFR-2.

Design, synthesis and molecular modeling of new 4-phenylcoumarin derivatives as tubulin polymerization inhibitors targeting MCF-7 breast cancer cells

A new set of 4-phenylcoumarin derivatives was designed and synthesized aiming to introduce new tubulin polymerization inhibitors as anti-breast cancer candidates. All the target compounds were evaluated for their cytotoxic effects against MCF-7 cell line, where compounds 2f, 3a, 3b, 3f, 7a and 7b, showed higher cytotoxic effect (IC50 = 4.3-21.2 μg/mL) than the reference drug doxorubicin (IC50 = 26.1 μg/mL), additionally, compounds 1 and 6b exhibited the same potency as doxorubicin (IC50 = 25.2 and 28.0 μg/mL, respectively). The thiazolidinone derivatives 3a, 3b and 3f with potent and selective anticancer effects towards MCF-7 cells (IC50 = 11.1, 16.7 and 21.2 μg/mL) were further assessed for tubulin polymerization inhibition effects which showed that the three compounds were potent tubulin polymerization suppressors with IC50 values of 9.37, 2.89 and 6.13 μM, respectively, compared to the reference drug colchicine (IC50 = 6.93 μM). The mechanistic effects on cell cycle progression and induction of apoptosis in MCF-7 cells were determined for compound 3a due to its potent and selective cytotoxic effects in addition to its promising tubulin polymerization inhibition potency. The results revealed that compound 3a induced cell cycle cessation at G2/M phase and accumulation of cells in pre-G1 phase and prevented its mitotic cycle, in addition to its activation of caspase-7 mediating apoptosis of MCF-7 cells. Molecular modeling studies for compounds 3a, 3b and 3f were carried out on tubulin crystallography, the results indicated that the compounds showed binding mode similar to the co-crystalized ligand; colchicine. Moreover, pharmacophore constructed models and docking studies revealed that thiazolidinone, acetamide and coumarin moieties are crucial for the activity. Molecular dynamics (MD) studies were carried out for the three compounds over 100 ps. MD results of compound 3a showed that it reached the stable state after 30 ps which was in agreement with the calculated potential and kinetic energy of compound 3a.