Azza T. Taher

Synthesis of novel isatin-thiazoline and isatin-benzimidazole conjugates as anti-breast cancer agents.

A series of new isatin-thiazoline 3a–h and isatin-benzimidazole 4a–h derivatives were synthesized via condensation of isatin Mannich bases 2a–h with either 2-aminothiazoline or 2-aminobenzimidazole. The structures of the newly synthesized compounds were characterized by spectral data. The anti-breast cancer activity of some of the synthesized compounds was assessed in the MCF-7 human breast cancer cell line. The results showed that compounds 4b, 4d and 4g possess significant antiproliferative activity against MCF-7 cells.

Synthesis and bioactivity evaluation of new 6-aryl-5-cyano thiouracils as potential antimicrobial and anticancer agents.

Several novel 6-aryl-5-cyano thiouracil derivatives were synthesized and explored for their activities as antibacterial, antifungal and anticancer agents. The antimicrobial evaluation revealed that compounds 7b and 7c possessed superior antibacterial activity against the Gram positive bacteria S. aureus and B. subtilis compared to the reference drug amoxicillin. Moreover, compound 4i was found to be a broad spectrum antimicrobial agent and it also exhibited the highest antifungal activity against C. albicans, even higher than the reference drug amphotericin B (MIC = 2.34, 3.00 μg/mL respectively). Selected compounds were tested for in vitro cytotoxicity at a single 10−5 M concentration in accordance to the NCI (USA) protocol. The preliminary screening results showed that most of the compounds had limited cytotoxic activity against renal cancer UO-31 and/or A498 cell lines. Nevertheless, compounds 6d and 6i displayed potent growth inhibitory effect toward non-small cell lung cancer HOP-92 and leukemia MOLT-4 cell lines, respectively.

Design, synthesis and cytotoxic activity of certain novel chalcone analogous compounds

A series of chalcone analogous compounds were designed and synthesized. Replacing/substituting the enone or ethylenic bridge of the parent chalcone with rigid heterocyclic moieties or substituted aromatic amines gave nineteen target compounds. Their cytotoxic activities were screened against both breast and liver cancer cells as well as breast and liver normal cells. Target compounds were also evaluated for their inhibition activity of tubulin beta polymerization. Target compound 2e, 3a, 3b, 3c, 4a-4d, 5a, 5b and 6 showed broad spectrum excellent anticancer activity against both MCF-7 and HepG2. Compound 4a showed the most TUBb inhibition activity.

Synthesis of new 1,3,4-benzotriazepin-5-one derivatives and their biological evaluation as antitumor agents

New derivatives of 1,3,4-benzotriazepin-5-one were designed and synthesized as structural analogues to the antitumor agents devazepide and asperlicin. An efficient and novel approach to the synthesis of 2-amino-1,3,4-benzotriazepin-5-one 2 was developed and its structure was confirmed. The newly synthesized derivatives were evaluated for their in vitro antitumor activity on 60 different cell lines. Compounds 8 and 9 displayed the most potent antitumor activity against several cell lines specifically ovarian cancer, renal cancer and prostate cancer, while compounds 5, 10 and 12 showed significant activities against UO-31 renal cancer cell line.

Synthesis of novel bis-anthraquinone derivatives and their biological evaluation as antitumor agents

Cancer has become a major worldwide problem and drug resistance now is one of the most important problems in treatment of cancer. Anthraquinone derivatives represent one of the most important drugs that can be used in treatment of many types of cancer. In this study two series of novel bis-anthraquinone derivatives have been synthesized. Five of these compounds were chosen to be evaluated for their antitumor activity against human cancer cell lines by the National Cancer Institute (NCI, USA). Marked activity was shown for the tested compounds(2–6). The most active one was compound 6 with mean value −67.00 against all cell lines. Compounds 7 and 8 were found inactive.Graphical Abstract.

Synthesis and Cytotoxic Activity of Certain Benzothiazole Derivatives Against Human MCF-7 Cancer Cell Line.

A new series of benzothiazole has been synthesized as cytotoxic agents. The new derivatives were tested for their cytotoxic activity toward the human breast cancer MCF‐7 cell line against cisplatin as the reference drug. Many derivatives revealed good cytotoxic effect, whereas four of them, 4, 5c, 5d, and 6b, were more potent than cisplatin, with IC50 values being 8.64, 7.39, 7.56, and 5.15 μm compared to 13.33 μm of cisplatin. The four derivatives’ cytotoxic activity was accompanied by regulating free radicals production, by increasing the activity of superoxide dismutase and depletion of intracellular reduced glutathione, catalase, and glutathione peroxidase activities, accordingly, the high production of hydrogen peroxide, nitric oxide, and other free radicals causing tumor cell death as monitored by reduction in the synthesis of protein and nucleic acids. Most of the tested compounds showed potent to moderate growth inhibitory activity; in particular, compound 6b exhibited the highest activity suggesting it is a lead compound in cytotoxic activity.

Synthesis and cytotoxic activity of certain trisubstituted azetidin-2-one derivatives as a cis-restricted combretastatin A-4 analogues

Novel series of 1,3,4-trisubstituted azetidin-2-one derivatives 8a–p were synthesized and proposed as cytotoxic agents acting via inhibition of tubulin at the colchicine binding site. The design of the target compounds was based upon modification in the structure of the vascular targeting agent combretastatin A-4 (CA-4). The cis double bond linker in CA-4 was replaced with the azetidin-2-one ring aiming to prevent the cis/trans isomerization that suppresses the activity of CA-4, thereby enhancing its antiproliferative activity. All new compounds were investigated in vitro against MCF-7 and HCT-116 cell lines. The inhibition of tubulin polymerization by four most potent compounds 8g, 8j, 8n and 8o was also evaluated. The synthesis of the final targets was achieved adopting Staudinger reaction. Molecular modeling studies were performed to rationalize the biological results.

A Clinico-Epidemilogical Study of Cases of Locally Advanced Non-Small Cell Lung Cancer (NSCLC) that Received Radiotherapy at NCI Cairo in the Period from 2001-2010

Purpose: This work was to study the clinic-epidemiological characteristics of patients with locally advanced NCSLC and to analyze their prognostic factors and also the results of different treatment modalities for local control and their effect on overall survival (OAS). Materials and methods: This is a retrospective study included 121 patients with primary locally advanced NSCLC diagnosed between 2001 and 2010 at the radiotherapy department, National Cancer Institute, Cairo University, Egypt. Results: The study showed significant correlation between the tumor size ≤ 7 cm, old age >60, moderately differentiated tumors G2 and treatment outcomes; better locoregional control and better survival rates. On the opposite side poorly differentiated tumors G3, tumor size >7 cm had the worst locoregional control and survival rates. The study also showed significant statistical correlation between treatment modality, locoregional control and survival rates. Patients who were treated by either concomitant chemo-radiotherapy or sequential chemoradiotherapy had better local control compared to other patients who were treated by radical radiotherapy, and they also had the best survival rates among all the other treatment groups. The average 6 months OAS rates for all studied patients were 60.3% while 12 months survival rates were 38.8%. The median OAS was 7 months. The data was summarized by descriptive statistics [i.e., mean, standard deviation (SD), frequencies]. Mean values and standard deviation were compared using simple T-test (2 variables). Percentages were compared using Chi-square test or Fisher’s exact test. Kaplan-Meier test was used for predictive survival rates. Conclusions: From the present study, we concluded that concomitant chemradiotherapy is the treatment of choice for locally advanced non small cell lung cancer; also we concluded that better performance status and higher hemoglobin levels have better treatment outcome in these cases.

Synthesis and binding study of certain 6-arylalkanamides as molecular probes for cannabinoid receptor subtypes

Tetrahydrocannabinol and other mixed cannabinoid (CB) receptors CB1/CB2 receptor agonists are well established to elicit antinociceptive effects and psychomimetic actions, however, their potential for abuse have dampened enthusiasm for their therapeutic development. In an effort to refine a semi-rigid structural framework for CB2 receptors binding, we designed novel compounds based on aromatic moiety and flexible linker with various amides mimicking the outlook of the endogenous anandamide which could provide as CB2 receptor ligand. In this direction, we developed and synthesized new aryl or arylidene hexanoic acid amides and aryl alkanoic acid diamide carrying different head groups. These new compounds were tested for their affinities for human recombinant CB receptors CB1 and CB2 and fatty acid amide hydrolase. Although, the preliminary screening of these compounds demonstrated weak binding activity towards CB receptor subtypes at 10 µmole, yet this template still could serve up as probes for further optimization and development of affinity ligand for CB receptors.