Mehmet Alp

Synthesis and Potent Antimicrobial Activity of Some Novel N-(Alkyl)-2-Phenyl-1H-Benzimidazole-5-Carboxamidines

A series of 22 novel 1,2-disubstituted-1H-benzimidazole-N-alkylated-5-carboxamidine derivatives were synthesized and evaluated for in vitro antibacterial activity against S. aureus and methicillin resistant S. aureus (MRSA), E. coli, E. faecalis and for antifungal activity against C. albicans. Compound 59 [1-(2,4-dichlorobenzyl)-N-(2-diethylaminoethyl)-1H-benzimidazole-5-carboxamidine], with a 3,4-dichlorophenyl group at the C-2 position, displayed the greatest activity (MIC = 3.12 μg/mL against both some bacteria and the fungus C. albicans).

Viscocanalostomy with mitomycin-C: a preliminary study.

Purpose To compare the results of viscocanalostomy with and without mitomycin-C (MMC). Methods Retrospective results of 15 standard viscocanalostomy (VCO) operations (Group 1) were compared with the prospective results of 15 VCO operations performed with intraoperative adjunctive MMC (Group 2). MMC (0.2 mg/mL) was applied over and under the superficial scleral flap for 3 minutes in Group 2 before the deep flap was prepared. Each patient was followed up for at least 1 year, and results of examinations in the first 12 months were used in the statistical comparison of the two groups. Surgical success was defined as intraocular pressure (IOP) ≤ 18 mmHg. Results Pr eoperative mean intraocular pressures (IOP) in Group 1 and Group 2 wer e 35.3±11.0 and 39.1±8.9, respectively. Mean IOP levels at the 12th month were 14.4±2.6 and 11.9±4.0, respectively, showing a significant decrease in both groups (p<0.001). Postoperative IOP course appeared to be lower in the MMC group, however, the difference was not statistically significant (p=0.554). Complete success rates without medications were 40% in Group 1 and 67% in Group 2. No significant difference was found between the two groups in terms of early and late postoperative complications, pre- and postoperative number of antiglaucoma medications, and surgical success rates at the end of the study period (p>0.05 for all). A significant difference was verified between the two groups of eyes considering the conjunctival bleb types, as low-lying, localized blebs were the most frequent type in Group 1 and thin-walled, avascular blebs were more predominant in the MMC group (p=0.004). Conclusions Intraoperative adjunctive MMC use might improve the long-term results of viscocanalostomy by facilitating subconjunctival filtration and might widen the indication range of the technique.

Immune recovery uveitis associated with highly active antiretroviral therapy in a patient with CMV retinitis and AIDS despite a low CD4+ T cell count: case report and a review of the literature

An unusual case of CMV retinitis and AIDS who developed immune recovery uveitis (IRU) despite a low CD4+ T cell count achieved during HAART is reported. A 36-year-old female complained of blurred vision in both eyes six months after initiation of anti-CMV retinitis therapy and HAART. Ocular examination revealed a substantial intraocular inflammation causing a dense vitreous haze and frosted branch angiitis. Consecutive CD4+ T cell counts were 20 cells/mm3 or less and plasma HIV mRNA was undetectable. The laboratory test for Cytomegalovirus was positive whereas those for infections known to cause uveitis were negative. The inflammatory reaction resolved with treatment, but she developed retinal detachment just before she died of pulmonary complications. A review of the literature led us to propose that our patient developed an intraocular inflammation which may probably be a form of IRU and it might be appropriate to employ additional criteria in the definition and the diagnosis of IRU.

Bis-benzimidazole hits against Naegleria fowleri discovered with new high throughput screens

ABSTRACT Naegleria fowleri is a pathogenic free-living amoeba (FLA) that causes an acute fatal disease known as primary amoebic meningoencephalitis (PAM). The major problem for infections with any pathogenic FLA is a lack of effective therapeutics, since PAM has a case mortality rate approaching 99%. Clearly, new drugs that are potent and have rapid onset of action are needed to enhance the treatment regimens for PAM. Diamidines have demonstrated potency against multiple pathogens, including FLA, and are known to cross the blood-brain barrier to cure other protozoan diseases of the central nervous system. Therefore, amidino derivatives serve as an important chemotype for discovery of new drugs. In this study, we validated two new in vitro assays suitable for medium- or high-throughput drug discovery and used these for N. fowleri. We next screened over 150 amidino derivatives of multiple structural classes and identified two hit series with nM potency that are suitable for further lead optimization as new drugs for this neglected disease. These include both mono- and diamidino derivatives, with the most potent compound (DB173) having a 50% inhibitory concentration (IC50) of 177 nM. Similarly, we identified 10 additional analogues with IC50s of <1 μM, with many of these having reasonable selectivity indices. The most potent hits were >500 times more potent than pentamidine. In summary, the mono- and diamidino derivatives offer potential for lead optimization to develop new drugs to treat central nervous system infections with N. fowleri.

Synthesis and potent in vitro activity of novel 1H-benzimidazoles as anti-MRSA agents.

A new class of 1H‐benzimidazolecarboxamidines was synthesized and evaluated for in vitro antibacterial and antifungal activities, including drug‐resistant bacterial strains. The most potent compound (32) has the same ratio of anti‐MRSA activity as Vancomycin (minimal inhibitory concentrations value 0.78 μg/mL). The mechanism of action for 1H‐benzimidazolecarboxamidine appears to be different from existing antibacterial agents. These compounds have potential for development as a new class of potent anti‐MRSA agent.

The evaluation of the retrobulbar orbital fat tissue and optic nerve with strain ratio elastography

AIM The aim of this study was to evaluate the diagnostic performance of strain ratio elastography in the assessment of retrobulbar orbital fat tissue. MATERIALS AND METHODS The retrobulbar fat tissue of 14 eyes in 14 participants was scanned by sonoelastography. All the participants had permanent vision loss secondary to glaucoma in at least one eye. The elasticity scores were determined and the strain ratio was based on the comparison of the average strain measured in the retrobulbar fat tissue around the optic nerve at the same depth. RESULTS The mean strain values for the optic nerve (B) and the retrobulbar fat tissue (A) were 0.78+/-0.61 and 1.43+/-0.99, respectively (p=0.005). The mean strain ratio (B/A) was 0.56+/-0.24. CONCLUSION This preliminary study showed that by providing strain values and ratios of different orbital tissues sonoelastography may have a potential use in the diagnosis and follow-up of orbital inflammatory and infiltrative diseases.

Synthesis and anticancer effects of some novel 2-(4-phenoxyphenyl)-1H-benzimidazole derivatives on K562 cell line

A series of novel 2-(4-phenoxyphenyl)-1H-benzimidazole derivatives was synthesized and tested in vitro on human chronic myelogenous leukemia (CML) cell line K562. Benzimidazoles containing 5-amidino (10), 5-N-isopropylamidino (11), 5-bromo (13), and 5,6-dimethyl (14) derivatives exhibited remarkable cytotoxic activity. The quantitative analysis of apoptosis by flow-cytometry demonstrated that the percentages of early and late apoptotic K562 cells treated with these compounds were significantly higher than cells without treatment. We also investigated the effects of these compounds on the expression of apoptosis-related genes BAX, BCL-2, BAD and BIM. Treatment of K562 cells wih compounds 10–14 significantly increased the expression levels of the proapoptotic genes BAX, BAD and BIM, whereas compound 20 increased BAX and BAD.

Ultrasound biomicroscopic evaluation of the efficacy of a transillumination technique for ciliary sulcus localization in transscleral fixation of posterior chamber intraocular lenses.

PURPOSE: To evaluate the efficacy of the transillumination technique for precisely locating the ciliary sulcus in transscleral fixation of posterior chamber intraocular lenses (PC IOLs) by determining the haptic positions with ultrasound biomicroscopy (UBM). SETTING: Department of Ophthalmology, Numune Training and Research Hospital, Ankara, Turkey. METHODS: Ultrasound biomicroscopy was used to determine the haptic positions in eyes with ab externo transsclerally fixated PC IOLs. Eyes were randomly assigned to a control group, in which transscleral fixation of a PC IOL was performed, or an endoilluminator‐assisted group, in which transscleral fixation was combined with transillumination. RESULTS: The study evaluated 33 eyes of 28 patients ranging in age from 16 to 81 years. The control group comprised 19 eyes (17 patients) and the endoilluminator‐assisted group, 14 eyes (12 patients). All haptics were easily visualized with UBM. The UBM examination showed that the rate of haptics located in the sulcus was statistically significantly higher in the endoilluminator‐assisted group (64%) than in the control group (24%) (P = .001). There was no significant difference in either group in the rate of precise sulcus location between the straight needle and the 28‐gauge insulin needle (P>.05). CONCLUSIONS: Ultrasound biomicroscopy showed the difficulty in reliably suturing the haptics in the ciliary sulcus, even with the use of a transillumination technique. However, the results suggest that the transillumination technique is a safe and easy procedure and helps the surgeon identify the ciliary sulcus during transscleral fixation of PC IOLs more precisely than without the use of transillumination.

Single-suture scleral fixation of subluxated foldable intraocular lenses

Purpose To evaluate the results of single-suture scleral fixation of subluxated foldable intraocular lenses (IOL) in eyes with sufficient residual capsular support. Methods The results of IOL repositioning by single-suture scleral fixation in 6 eyes of 6 patients with IOL subluxation were included. All subluxated IOLs were single-piece hydrophilic acrylic. Subluxation resulted from posterior capsule tears in 3 eyes, zonular dialyses in 2 eyes, and zonular dialysis with a capsulorhexis tear in 1 eye. A similar technique was used in all eyes in which one haptic was externalized through a superior clear corneal incision and tied with a Pair-PAK 10-0 polypropylene suture, and was finally retracted and fixated behind the iris close to the ciliary sulcus at the 12:00 meridian. All patients were followed up for at least 6 months. Results Best-corrected visual acuities ranged between finger counting and 20/70 (mean logMAR 1.02±0.64) preoperatively, and between 20/100 and 20/20 (mean logMAR 0.22±0.26) at the final postoperative visit. All IOLs remained centered and no significant postoperative complications were encountered except for an IOL tilt which resulted in a considerable oblique astigmatism in one eye. Conclusions Subluxated foldable IOLs may safely be repositioned and secured with a single scleral fixation suture in selected cases with adequate amount of capsular remnants.

Synthesis and cytotoxic evaluation of novel N-substituted amidino-1-hydroxybenzimidazole derivatives.

A new class of N-substituted amidino-1-hydroxybenzimidazole derivatives (15–24) were synthesized and evaluated for their in vitro cytotoxic activities against human leukemia cell lines, HL-60 and K562. The preliminary results showed that compounds 16, 20, 21 and 23 had moderate antitumor activity against HL-60 cell line. Further investigation on the mechanism of the observed cytotoxic effects demonstrated that compound 21 increased the expression of autophagic and apoptotic genes and induced apoptosis of HL-60 cells.