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

Alp, Mehmet,Goker, Hakan,Ozkan, Tulin,Sunguroglu, Asuman 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

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.

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

Mehmet Alp,Hakan Go¨ker,Tulin Ozkan,Asuman Sunguroglu 대한약학회 2014 Archives of Pharmacal Research Vol.37 No.5

A new class of N-substituted amidino-1-hydroxybenzimidazole derivatives (15–24) were synthesizedand evaluated for their in vitro cytotoxic activitiesagainst human leukemia cell lines, HL-60 and K562. Thepreliminary results showed that compounds 16, 20, 21 and23 had moderate antitumor activity against HL-60 cell line. Further investigation on the mechanism of the observedcytotoxic effects demonstrated that compound 21 increasedthe expression of autophagic and apoptotic genes andinduced apoptosis of HL-60 cells.

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

A. Selen Gurkan-Alp,Hakan Go¨ker,Mehmet Alp,Tulin Ozkan,Asuman Sunguroglu 대한약학회 2015 Archives of Pharmacal Research Vol.38 No.5

A series of novel 2-(4-phenoxyphenyl)-1Hbenzimidazolederivatives was synthesized and testedin 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 cytotoxicactivity. The quantitative analysis of apoptosis by flowcytometrydemonstrated that the percentages of early andlate apoptotic K562 cells treated with these compoundswere significantly higher than cells without treatment. Wealso investigated the effects of these compounds on theexpression of apoptosis-related genes BAX, BCL-2, BADand BIM. Treatment of K562 cells wih compounds 10–14significantly increased the expression levels of the proapoptoticgenes BAX, BAD and BIM, whereas compound20 increased BAX and BAD.

Cardiovascular Disease Risk in Children and Adolescents with Attention Deficit/Hyperactivity Disorder

Necati Uzun(Necati Uzun ),Mehmet Akif Akıncı(Mehmet Akif Akıncı ),Hayrullah Alp(Hayrullah Alp ) 대한정신약물학회 2023 CLINICAL PSYCHOPHARMACOLOGY AND NEUROSCIENCE Vol.21 No.1

Objective: The aim of this case-controlled study is to evaluate chronic inflammation, subclinical atherosclerosis and cardiovascular disease risk in children and adolescents with ADHD. Methods: A total of 51 medication-free children and adolescents with ADHD and 51 healthy controls were included in this study. K-SADS-PL was used to determine the diagnosis of ADHD and other psychiatric disorders. Conners’ Parent Rating Scale-Revised Short Form and the Conners’ Teacher Rating Scale-Revised Short Form severity of ADHD was used to evaluate severity of ADHD. In order to evaluate subclinical atherosclerosis, common carotid intima media thickness (IMT), epicardial adipose tissue thickness (EAT), and periaortic adipose tissue thickness (PAT) were assessed as well as clinical parameters. Results: The IMT (0.037 ± 0.005 cm vs. 0.026 ± 0.003 cm), EAT (0.472 ± 0.076 cm vs. 0.355 ± 0.051 cm), and PAT (0.135 ± 0.016 cm vs. 0.118 ± 0.009 cm) measurements were significantly higher in the ADHD group than in the control group. Additionally, partial correlation analyses revealed that a positive correlation was observed between IMT and EAT, and PAT measurements separately. Multivariate linear regression analysis revealed that, body mass index (BMI) positively predicted IMT. Also, age and BMI positively predicted the EAT levels of the subjects with ADHD. Conclusion: Our results suggest that children and adolescents with ADHD have a risk for cardiovascular disease. For this reason, subclinical atherosclerosis should be taken into consideration in the follow-up and treatment of ADHD for cardiovascular disease risk.

Obesity does not affect the number of retrieved lymph nodes and the rate of intraoperative complications in gynecologic cancers

Mehmet Coskun,Alp Usubutun,Tulay Ozlu,Kubra Boynukalin,Kunter Yuce 대한부인종양학회 2010 Journal of Gynecologic Oncology Vol.21 No.1

Objective: Lymphadenectomy, in general, is a safe and well-tolerated procedure in gynecologic oncology. However,some technical difficulties may be experienced in obese women which may result in inadequate lymphadenectomy and increased complications. The purpose of this study is to retrospectively evaluate the effect of obesity on lymph node counts retrieved and complication rates observed during lymphadenectomy in gynecologic cancers. Methods: Patients with ovarian, endometrial or cervical cancers treated with initial surgery including bilateral pelvic and paraaortic lymph node dissection were grouped as non-obese and obese. These two groups were compared in terms of the number of retrieved lymph nodes and the rate of intraoperative complications directly related to lymph node dissection. Results: One hundred twenty-three patients were eligible with a mean age of 55.1 years and mean body mass index of 29.2 kg/m2. Fifty-nine patients were obese while 64 were non-obese. Lymph node counts obtained in different stations and in total were similar among non-obese and obese patients. Rates of lymphadenectomy-related intraoperative complications including vascular, neural, intestinal, and bladder injury were also similar in non-obese and obese patients. Conclusion: The obesity does not affect the lymph node counts and intraoperative complication rates adversely in women with gynecologic cancers. Therefore, adequate lymph node dissection should not be omitted based solely upon obesity in gynecologic oncology patients.

Comparison of WHO and endometrial intraepithelial neoplasia classifications in predicting the presence of coexistent malignancy in endometrial hyperplasia

Mehmet Coskun Salman,Alp Usubutun,Kubra Boynukalin,Kunter Yuce 대한부인종양학회 2010 Journal of Gynecologic Oncology Vol.21 No.2

Objective: The most commonly used classification system for endometrial hyperplasia is the World Health Organization system which is based on subjective criteria. Another classification system is endometrial intraepithelial neoplasia (EIN) system which uses diagnostic criteria including cytological demarcation, crowded gland architecture,minimum size of 1 mm, and careful exclusion of mimics, and aims to identify a precancer or cancer. The objective of this study was to compare the two classification systems in terms of predicting the presence of a coexistent cancer in surgically treated patients. Methods: Biopsy and hysterectomy specimens of 49 women who were subjected to surgery with a preoperative diagnosis of endometrial hyperplasia (EH) according to the WHO system were re-evaluated retrospectively by using EIN system. Results: Among the 49 patients, 69.4% had complex atypical EH and 75.5% had EIN at biopsy specimens. EIN was detected in 94.1% of complex atypical EH, and 41.7% of non-atypical EH. Nine women (18.4%) had endometrial cancer. Among women with cancer, all had complex atypical EH or EIN. The rate of coexistent endometrial cancer was 26.5% in women with complex atypical EH and 24.3% in women with EIN. Conclusion: Diagnoses of atypical or complex atypical EH and EIN had similar sensitivities and negative predictive values in predicting the coexistent endometrial cancer. Either of these two classification systems may be used safely when an experienced pathologist is available. However, use of the objective EIN system may be preferred whenever possible to prevent diagnostic errors in centers where an experienced pathologist is not available.

Evaluation of the Effects of the Flavonoid Apigenin on Apoptotic Pathway Gene Expression on the Colon Cancer Cell Line (HT29)

Mehmet Turktekin,Ece Konac,H. Ilke Onen,Ebru Alp,Akin Yilmaz,Sevda Menevse 한국식품영양과학회 2011 Journal of medicinal food Vol.14 No.10

Apigenin (4′,5,7-trihydroxyflavone) is one of the leading components supporting targeted treatment options. We explored the cytotoxic and apoptotic effects of various doses of apigenin administered alone and together with 5-fluorouracil (5-FU)—a chemotherapeutic agent with high cytotoxicity—for different incubation periods, on morphologic, DNA, RNA (messenger RNA [mRNA]), and protein levels on the p53 mutant HT29 human colon adenocarcinoma cell line. Treatment with apigenin alone for a 72-hour incubation at 90-μM dose resulted in an apoptotic percentage of 24.92% (P=.001). A higher percentage (29.13%) was observed after treatment with the same dose of apigenin plus 5-FU for the same incubation period (P=.001). These results were confirmed as mRNA and protein expression levels of caspase-3 increased 2.567-fold and mRNA expression levels of caspase-8 increased 3.689-fold compared with the control group. On the other hand, mRNA expression levels of mammalian target of rapamycin (mTOR) and cyclin D1 (CCND1) decreased by 0.423-fold and 0.231-fold, respectively. To our knowledge this is the first study showing that treatment with apigenin alone results in cell cycle arrest through activation of caspase cascade and stimulation of apoptosis in HT29 cells. It also shows that use of apigenin plus 5-FU further increases this effect. This study draws attention to the probable clinical effectiveness of apigenin plus a chemotherapeutic agent with high cytotoxicity. It also highlights the induction of desirable apoptotic effects by targeting the caspase cascade pathway through administration of reduced doses for shorter incubation periods.

Lipoleiomyoma of broad ligament mimicking ovarian cancer in a postmenopausal patient: case report and literature review

Mehmet Coskun Salman,Alp Usubutun,Kunter Yuce,Zeliha Atak 대한부인종양학회 2010 Journal of Gynecologic Oncology Vol.21 No.1

Lipoleiomyoma is a very rare tumor which is composed of adipocytes and smooth muscle cells. It is most commonly located in uterine corpus although cervical, ovarian, and retroperitoneal locations were also reported. Lipoleiomyoma located in broad ligament is extremely uncommon and only five cases were reported to date. Here, we report the sixth case of lipoleiomyoma of broad ligament which was diagnosed in a postmenopausal woman who was subjected to exploratory laparotomy with a preoperative diagnosis of a solid adnexal mass suggesting an ovarian malignancy.

Comparison of the Effects of Electroacupuncture and Melatonin on Nerve Regeneration in Experimentally Nerve-Damaged Rats

Yasemin Özkan,Mehmet Turgut,Yasemin Turan,Mehmet Dinçer Bilgin,Sinem Sari,Mustafa Yilmaz,Yiğit Uyanikgil,Mahmut Alp Kiliç,Derya Tanriöver,Zehra Seznur Kasar 사단법인약침학회 2021 Journal of Acupuncture & Meridian Studies Vol.14 No.5

Background: Development of methods to accelerate nerve regeneration in peripheral nerve damage is important. Electroacupuncture is a new therapeutic method that combines traditional acupuncture with modern electrotherapy. Melatonin has been shown to reduce nerve damage. Objectives: In this study, we aimed to determine and compare the therapeutic effects of electroacupuncture and melatonin on rat sciatic nerve injury. Methods: A total of 56 adult male Wistar Albino rats were divided into four study groups with 14 animals in each group: intact control (group I), subcutaneous saline (group II), subcutaneous melatonin (group III), and electroacupuncture (group IV). Surgical procedure including unilateral (right) sciatic nerve injury was applied to groups II, III, and IV. Saline and melatonin started immediately after surgery for six weeks, while electroacupuncture was given two weeks after surgery for 3 weeks. Functional and histological assessments were used as outcome measurements. Results: Sciatic nerve damage caused a significant decrease in nerve conduction velocity. Both electroacupuncture treatment and melatonin treatment significantly increased the nerve conduction velocity. Both sciatic functional recovery and histological regeneration were faster in these treatment groups compared to the saline. However, no significant difference was observed between the two treatment groups. Conclusion: Electroacupuncture and melatonin are promising alternative treatment strategies for peripheral nerve damage and can be examined in detail in future studies.

Peroxidase gene markers revealed genetic diversity and population structure in okra germplasm

Yildiz Mehtap,Furan Mehmet Alp,Koçak Metin,Sadık Gökhan,Kuzğun Cansu,Al-Khafaji Mahdi,Bahjat Noor Maiwan 한국식물생명공학회 2022 Plant biotechnology reports Vol.16 No.2

Okra is a widely grown vegetable crop in various regions of the world and provides significant amounts of vitamins and minerals. Numerous researchers have documented the efficacy of phenotypic and molecular classification of the diverse okra germplasm collections found throughout the world. The genetic variation of Turkish okra germplasm, which included 39 genotypes, was characterized using 14 POGP (peroxidase gene polymorphism) primer pairs in comparison to other world okra genotypes and accessions, which contained 27 genotypes. A total of 84 bands were generated using 14 POGP primer pairs, with 43 (51%) of them being polymorphic between okra accessions. The values of polymorphism information content ranged from 0.03 to 0.99, with an average of 0.48. The range and mean values for gene diversity (h) were 0.03–0.42 and 0.25, respectively. Shannon’s information index (I) varied between 0.07 and 0.62 for each POGP marker, with a mean of 0.40. The most divergent genotypes were found to have a GS value of 0.23, with IN-7 and TR20-3 being the genetically most distant. The STRUCTURE, PCoA and Neighbor-joining analysis separated the okra germplasm into three populations. AMOVA revealed 23 and 77% variance across and within populations, respectively. Although the germplasm of okra is generally homogenous, the influence of shared genes is more significant. For the first time, the genetic composition of okra was determined using peroxidase gene markers.