فهرست مطالب sussan kabudanian ardestani

Human papillomavirus (HPV) is a primary contributing agent of cervical cancer. Eradication of HPV-related infections requires therapeutic strategies. We used Brucella abortus RB51 rough lipopolysaccharide (R-LPS) as an adjuvant along with two HPV16 therapeutic DNA vaccines, pcDNA3-E7 and pcDNA3-L1, for improving DNA vaccine efficacy. For evaluation of the B. abortus LPS adjuvant efficacy in combination with DNA vaccines to induce cellular immune responses, C57BL/6 mice were immunized with the DNA vaccines, with or without R-LPS adjuvant. IFN-γ and IL-4 cytokines assay was carried out for assessment of cellular and humoral immune responses.   Findings indicated that vaccination with pcDNA3-E7 or pcDNA3-L1 alone could induce strong cellular immune responses, but stronger antigen-specific T-cell immune responses were shown by co-administration of HPV16 E7 and HPV16 L1 DNA vaccines along with R-LPS adjuvant. Overall, B. abortus R-LPS through enhancement of T-cell immune responses can be considered an efficient vaccine adjuvant in future studies and trials.

In this study, a series of novel compounds based on 5-(5-nitrothiophene-2-yl)-1,3,4-thiadiazole possessing (het)aryl thio pendant at C-2 position of thiadiazole ring is developed and evaluated as antileishmanial agents using MTT colorimetric assay. 10 New compounds containing aryl and hetero aryl derivatives, started from thiophene-2-carbaldehyde in five steps, were synthesized in good to excellent yields and characterized by 1H-NMR, 13C-NMR and IR spectroscopy. Through the compounds 6a-j, methylimidazole containing derivative 6e was recognized as the most active compound against L. major promastigotes exhibiting IC50 values of 11.2µg/ml and 7.1µg/ml after 24 and 48 hours, respectively. This compound is >4 fold more effective than Glucantime as a standard drug (IC50 = 50 µg/ml after 24 h and 25 µg/ml after 48 h).

A series of (5-nitrofuran-2-yl)-1, 3, 4-thiadiazole-2-yl derivatives 6a–6e have been synthesized and screened for in vitro anti-leishmanial activity against the promastigote form of L. major. The structure of Schiff bases were confirmed by 1H NMR, IR. Screening results indicate that all of the designed and synthesized final compounds (6a-6e) significantly reduced the viability of promastigotes of L. major in comparison to glucantime (IC50 3× 103 μg/ml). Meta and Para substitutions in benzene ring containing compounds were more potent than other derivative and the most potent compounds were 6d, 6e with IC50 value 94 µM and 77.6 µM, respectively. The experimental data proposes that (5-nitrofuran-2-yl)-1, 3, 4-thiadiazole-2-yl derivatives may be further investigated as a candidate drug for treatment of cutaneous leishmaniasis.

Matrix metalloproteinases (MMPs) are a family of proteinases and have the vigorous capacity to degrade all parts of the extracellular matrix. MMP enzymes strongly participate in physiological processes such as normal tissue remodeling and wound healing and in pathology of pulmonary diseases. They are released in response to environmental stimuli such as toxins and regulated by endogenous tissue inhibitors of metalloproteinases (TIMPs). Sulfur mustard (SM) is a chemical toxic which can cause severe permanent damages to lung tissues. The aim of this study was assessing the possible role of MMP-9 and TIMPs in SM-induced lung symptoms and signs in exposed patients 20 years after exposure.
Totally, 372 male volunteers with a history of SM exposure and 128 age- and sex-matched unexposed controls participated and were divided into three groups: normal, mild and moderate-severe. All participants underwent clinical evaluation and pulmonary function tests and serum concentrations of MMP-9 and its inhibitors were measured using the ELISA technique.
Serum level of MMP-9 was increased in the SM exposed group who had moderate-severe pulmonary complications compared with the SM exposed with normal lung (2.321 ± 2.836 vs. 1.546 ± 2.176, P = 0.001) while only the MMP-9/TIMP-4 complex was elevated in the SM exposed with normal lung individuals compared to its corresponding control group (85 ± 265 vs. 82 ± 222, P = 0.025). Although MMP-9 and its inhibitors did not show any correlation with spirometry findings, elevated circulating MMP-9 was detected in SM exposed patients with chronic chough and hemoptysis (P = 0.013 and P = 0.013 respectively).
High level of tissue disruption and remodeling mediators could influence lung structure in long-term after SM exposure. The correlation of clinical evaluation with these factors efficiently helps us to identify important effectors.

Quinolone antibacterials are one of the most important classes of pharmacological agents known as potent inhibitors of bacterial DNA gyrase and topoisomerase IV that efficiently inhibit DNA replication and transcription by generating several double-stranded DNA break. Some quinolone derivatives demonstrated inhibitory potential against eukaryote topoismarase II and substantial dose-dependent cytotoxic potential against some cancerous cells. In present study, synthesis and cytotoxic activity evaluation of new series of N-pipearzinyl quinolones containing N-2-(furyl-2 or 3-yl)-2-(chlorobenzyloxyimino) ethyl moiety 7a-i have been studied. Reaction of quinolone, with 2-bromo-1-(furan-2 or 3-yl)ethanone-O-substituted chlorobenzyloxime in DMF in presence of NaHCO3 at room temperature, gave the title compounds N-2-(furan-2 or 3-yl)-2-(chlorobenzyloxyiminoethyl) quinolone 7a-i. Synthesized compounds were further evaluated in-vitro against three human breast tumor cell lines. Preliminary screening indicated that compound 7 g demonstrated significant growth inhibitory potential against all evaluated cell lines. The results of structure-activity relationship study exhibited that quinolone derivatives are superior in cytotoxic potential compared to 1, 8-naphthyridone series. Furthermore, ethyl quinolone derivatives were more potent cytotoxic agents comparing with cyclopropyl quinolones.

Chalcones and their rigid analogues represent an important class of small molecules having anticancer activities. Therefore, in this study the synthesis and cytotoxic activity of new 3-benzylidenchroman-4-ones were described as rigid chalcone analogues. The reaction of resorcinol with 3-chloropropionic acid in the presence of CF3SO3H was afforded corresponding propiophenone. It was cyclized using 2M NaOH to give 7-hydroxy-4-chromanone. O-Alkylation of 7-hydroxy-4-chromanone with alkyl iodide in the presence of K2CO3 gave 7-alkoxychroman-4-one. Finally, condensation of chroman-4-one derivatives with different aldehydes afforded target compounds in good yields. The newly synthesized compounds were tested in vitro against different human cancer cell lines including K562 (human erythroleukemia), MDA-MB-231 (human breast cancer), and SK-N-MC (human neuroblastoma) cells. The cell viability was evaluated using MTT colorimetric assay. Most of the compounds showed good inhibitory activity against cancer cells. Among them, compound 4a containing 7-hydroxy group on chromanone ring and 3-bromo-4-hydroxy-5-methoxy substitution pattern on benzylidene moiety was the most potent compound with IC50 values ≤ 3.86 μg/ml. It was 6-17 times more potent than etoposide against tested cell lines. We described synthesis and cytotoxic activity of poly-functionalized 3-benzylidenechroman-4-ones as new chalcone-like agents. These compounds can be considered as conformationally constrained congeners of chalcones to tolerate the poly-functionalization on the core structures for further optimization.

The Leishmaniasis is a zoonotic disease that remains a severe public health problem and its burden is increasing. By now there is no anti-leishmaniasis vaccine and as other tripanosomial disease, is treated by limited drugs. First line drug includes pentavalent Antimony such as sodium stibogluconat and meglumine antimoniate that use of these drugs is limited due to side effects, long term treatment, high cost and incidence of drug resistance. It is clear that developing new, effective, cheap and safe drug is necessary for treating Leishmaniasis. In this study new four derivatives of 1-(5-halo-2-thienyl)-2-[5-(5-nitroheteroaryl)]-1,3,4-thiadiazol-2-ylthio)ethanone were synthesized and target compounds were evaluated against the promastigote form of Leishmania major using MTT assay in comparison with control drug (Fluconazole). Concentrations (5-150 µg/mL) of synthesized compounds and control drug were prepared and IC50 for each compound was measured. IC50 for 8a-d was 114.98 µM (44.59±8.15 µg/mL), 118.05 µM (51.25±9.08 µg/mL), 130.7 µM (52.78±12.97 µg/mL), and 252.7 µM (113.3±5.92 µg/mL) respectively that was less than of fluconazole 980 µM (300 µg/mL). The results of this study showed that four synthesized compounds had a significant effect on Leishmania major and have a stronger effect than control drug. It seems that these compounds can be used as an alternative in future.

Proliferation and apoptosis of lymphocytes are essential parts of the immune system. Most anti-cancer chemotherapy drugs such as vincristine target cell cycle and induce apoptosis in cancer cells. In other words, dividing cells undergo more apoptosis, which may also include the normal proliferating lymphocytes responsive to malignancies as well. In this study, the effect of different concentration of vincristine at three different time periods on resting and proliferating spleen lymphocytes were evaluated and compared with the effect of the drug on mouse lymphoma cell line BCL1. The cytotoxicity of vincristine was determined by MTT assay and IC50 was calculated for all periods. The cells were also stained with double staining acridine orange and ethidium bromide and were observed with fluorescence microscope and the percentage of apoptotic cells were determined. MTT results showed that vincristine at concentrations of 10 and 20 μg/ml caused cell death in both resting and proliferating lymphocytes, but concentrations<5 μg/ml did not show any significant cytotoxic effect, while concentrations of 2 and 5 μg/ml showed significant cytotoxic effect on BCL1 cells. The percentage of the apoptotic cells which were affected by different concentrations of the drug was proportional in the two methods, i.e. fluorescence microscope and MTT assay. Vincristine has a strong cytotoxic effect in tumor cells and its toxic effect in normal cells is highly dependent on time and the activation of the cells.