The importance of histomorphological features and ERG expression in the diagnosis of malignancy in cases with atypical small acinar proliferation.

BACKGROUND: Atypical small acinar proliferation (ASAP) cases typically require rebiopsy, which are invasive and associated with increased risk of complications. Our aim in this study was to determine the importance of laboratory and histological findings and E-26 transformation-specific-related gene (ERG) expression in the diagnosis of malignancy. METHODS: Between March 2016 and March 2022, 84 patients who were diagnosed with ASAP on biopsy or rebiopsy were included in the study. Clinical-laboratory features of age, serum prostate-specific antigen level, and histopathological features were compared and included multifocality, number of suspicious acini, nuclear enlargement, nucleolar prominence, hyperchromasia, cytoplasmic amphophilia, luminal amorphous acellular secretion, crystalloid presence, infiltrative appearance, inflammation, atrophy, α-methyl acyl-CoA racemase, p63, and/or high molecular weight cytokeratin were analyzed. In addition, ERG expression was evaluated immunohistochemically. RESULTS: Statistically significant correlation was found between nucleolar prominence, nuclear hyperchromasia, crystalloid presence, infiltrative pattern, and prostate cancer (p < .001). In 19 of 84 cases (22.6%) ERG was positive in the nucleus. Prostate cancer was diagnosed at rebiopsy in 15 of the 19 ERG-positive cases (78.9%). A statistically significant correlation was found between ERG positivity and prostate cancer (p= .002). CONCLUSIONS: Our findings suggest that evaluation of these markers during initial transrectal ultrasound biopsies may decrease and prevent unnecessary prostate rebiopsy.

Intramolecular Friedel-Crafts Reaction with Trifluoroacetic Acid: Synthesizing Some New Functionalized 9-Aryl/Alkyl Thioxanthenes.

In this study, a series of halogen-substituted thioxanthenes were synthesized because the most important and biologically active derivatives of xanthenes are thioxanthenes. In order to obtain new thioxanthene derivatives, first, the starting molecules were synthesized by the appropriate reaction methods in two steps. The intramolecular Friedel-Crafts alkylation (FCA) method was used to convert the prepared three aromatic substituted starting alcohol compounds to their corresponding thioxanthenes by cyclization. For the intramolecular FCA reaction of secondary alcohols, which are the starting compounds (1a-1t), organic BroÌ·nsted acids, which require more innovative, easier, and suitable reaction conditions, were used instead of halide reagents with corrosive effects as classical FCA catalysts. Trifluoroacetic acid was determined to be the organocatalyst with the best yield. Therefore, some original 9-aryl/alkyl thioxanthene derivatives (2a-2t) were synthesized using the optimized FCA method. In addition, a new sulfone derivative of thioxanthene 3i was prepared by performing the oxidation reaction with one of the obtained new thioxanthene 2i. Thioxanthenes and their derivatives are important heterocyclic structures that contain pharmacologically valuable sulfur and are used in the treatment of psychotic diseases such as Alzheimer's or schizophrenia, as well as a number of potent biological activities.

New Strategy for the Synthesis of Some Valuable Chiral 1,3-Diols with High Enantiomeric Purity: New Organocatalyst, Asymmetric Aldol Reaction, and Reduction.

Chiral 1,3-diols are highly valuable molecules used in industries such as pharmaceuticals, cosmetics, and agriculture. Therefore, in this study, a new strategy was developed to synthesize enantiomerically pure (>99% ee) 1,3-diols. New chiral 1,3-diols (5a-5q) with high enantiomeric purity were synthesized from aldol products chiral 1,3-keto alcohols (4a-4q), which are aldol products with different structures. Chiral 1,3-keto alcohols (4a-4q) were synthesized by a new asymmetric aldol method in the first step. This method was developed using a new proline-derived organocatalyst (3g) and Cu(OTf)2 as an additive in DMSO-H2O for the first time. Almost >99% ee was obtained using our developed aldol procedure. In the second step, original chiral diols (5a-5q) of high enantiomeric purity were obtained by asymmetric reduction of chiral keto alcohols with chiral oxazaborolidine reagents. In this way, a two-step asymmetric reaction was developed for chiral 1,3-diol enantiomers with high enantiomeric purity. The structures of all the original chiral compounds obtained were elucidated by infrared and nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis methods. Their enantiomeric excesses were determined by the chiral high-performance liquid chromatography method. Both keto alcohols and their corresponding chiral diols synthesized can be used as chiral starting materials and chiral source materials or intermediates in the synthesis of many biologically active molecules, or they can be used as chiral ligands in asymmetric synthesis, serving as organocatalysts.

Ethyl pyruvate attenuates cisplatin-induced ovarian injury in rats via activating Nrf2 pathway.

Although cisplatin (CDDP) is an antineoplastic drug widely used for the treatment of various tumors, its toxicity on the reproductive system is a concern for patients. Ethyl pyruvate (EP) possesses potent antioxidant and anti-inflammatory activities. The objective of this study was to evaluate the therapeutic potential of EP on CDDP-mediated ovotoxicity for the first time. Rats were exposed to CDDP (5 mg/kg) and then treated with two doses of EP (20 and 40 mg/kg) for 3 days. Serum fertility hormone markers were evaluated using ELISA kits. Oxidative stress (OS), inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were also determined. In addition, how CDDP affects the nuclear factor erythroid 2-associated factor 2 (Nrf2) pathway and the effect of EP on this situation were also addressed. EP improved CDDP-induced histopathological findings and restored decreasing levels of fertility hormones. EP treatment also reduced the levels of CDDP-mediated OS, inflammation, ERS and apoptosis. In addition, EP attenuated CDDP-induced suppression in the levels of Nrf2 and its target genes, including heme oxygenase-1, NAD(P)H quinone dehydrogenase-1, superoxide dismutase and glutathione peroxidase. Histological and biochemical results showed that EP can have therapeutic effects against CDDP-induced ovotoxicity with antioxidant, anti-inflammatory and Nrf2 activator activities.

Vanillic acid abrogates cisplatin-induced ovotoxicity through activating Nrf2 pathway.

Although cisplatin (CDDP) is an effective anticancer agent, the ovotoxicity that can occur in female patients limits its use. Oxidative stress (OS) and inflammation are known to contribute to CDDP-induced ovotoxicity. Vanillic acid (VA) is a dietary herbal secondary metabolite with high free radical scavenging activity. It was aimed to evaluate the therapeutic effects of VA against CDDP-induced ovotoxicity in rats in this study for the first time. Ovotoxicity was achieved with a single dose of CDDP (5 mg/kg) in female rats. The therapeutic effect of VA was evaluated with 3-day administration of two different doses (5 and 10 mg/kg). While OS, inflammation, endoplasmic reticulum stress (ERS) and apoptosis markers were measured in tissue samples, the levels of reproductive hormones were determined in serum samples using colorimetric methods. The results showed that CDDP-induced nuclear factor erythroid 2-associated factor 2 (Nrf2) inhibition combined with increased OS, inflammation, ERS and apoptosis increased ovarian damage. VA treatments reversed these changes via activating Nrf2 pathway dose-dependently. In addition, histopathological findings also supported the biochemical results. VA may be a good therapeutic molecule candidate for CDDP-induced ovarian damage due to strong antioxidant and Nrf2 activator properties.

The therapeutic effect of silibinin against 5-fluorouracil-induced ovarian toxicity in rats.

5-Fluorouracil (5-FU) is a fluoropyrimidine group antineoplastic drug with antimetabolite properties and ovotoxicity is one of the most important side effects. Silibinin (SLB) is a natural compound that is used worldwide and stands out with its antioxidant and anti-inflammatory properties. The aim of this study was to evaluate the therapeutic effect of SLB in 5-FU-induced ovototoxicity using biochemical and histological analysis. This study was carried out in five main groups containing six rats in each group: control, SLB (5 mg/kg), 5-FU (100 mg/kg), 5-FU + SLB (2.5 mg/kg), and 5-FU + SLB (5 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase (SOD), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), tumor necrosis factor-alpha (TNF-α), myeloperoxidase (MPO), and caspase-3 were determined using spectrophotometric methods. Hematoxylin and eosin staining method was employed for histopathological examination. MDA, TOS, 8-OHdG, TNF-α, MPO, and caspase-3 levels in 5-FU group were significantly increased compared with the control group, while the levels of TAS, SOD, and CAT were decreased (p < 0.05). SLB treatments statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the 5-FU group compared with the control group, SLB treatments also statistically significantly restored these damages (p < 0.05). In conclusion, SLB has a therapeutic effect on the ovarian damage induced by 5-FU via decreasing the levels of oxidative stress, inflammation, and apoptosis. It may be helpful to consider the usefulness of SLB as an adjuvant therapy to counteract the side effects of chemotherapy.

Novel N-Acyl Hydrazone Compounds as Promising Anticancer Agents: Synthesis and Molecular Docking Studies.

In this study, a new series of N-acyl hydrazones 7a-e, 8a-e, and 9a-e, starting from methyl δ-oxo pentanoate with different substituted groups 1a-e, were synthesized as anticancer agents. The structures of obtained target molecules were identified by spectrometric analysis methods (FT-IR, 11H NMR, 13C NMR, and LC-MS). The antiproliferative activity of the novel N-acyl hydrazones was evaluated on the breast (MCF-7) and prostate (PC-3) cancer cell lines by an MTT assay. Additionally, breast epithelial cells (ME-16C) were used as reference normal cells. All newly synthesized compounds 7a-e, 8a-e, and 9a-e exhibited selective antiproliferative activity with high toxicity to both cancer cells simultaneously without any toxicity to normal cells. Among these novel N-acyl hydrazones, 7a-e showed the most potent anticancer activities with IC50 values at 7.52 ± 0.32-25.41 ± 0.82 and 10.19 ± 0.52-57.33 ± 0.92 µM against MCF-7 and PC-3 cells, respectively. Also, molecular docking studies were applied to comprehend potential molecular interactions between compounds and target proteins. It was seen that the docking calculations and the experimental data are in good agreement.

Arbutin abrogates testicular ischemia/reperfusion injury in rats through repression of inflammation and ER stress.

The aim of this study was to investigate the effects of arbutin (ARB) administration on oxidative stress, inflammation, endoplasmic reticulum (ER) stress and apoptosis in an experimental testicular torsion/detorsion (T/D)-induced testicular injury model for the first time. A total of 24 male Sprague-Dawley rats were divided into four groups with six rats in each group: sham control, T/D, T/D+ARB (50 mg/kg) and T/D+ARB (100 mg/kg). Torsion and detorsion times were applied as 4 h and 2 h, respectively. The levels of lipid peroxidation [malondialdehyde (MDA)] and oxidative stress [total oxidant status (TOS) and total antioxidant status (TAS)] in testicular tissues were determined using colorimetric methods. The levels of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], antioxidant system [superoxide dismutase (SOD) and catalase (CAT)], pro-inflammatory cytokines [high mobility group box 1 (HMGB1), nuclear factor kappa B protein 65 (NF-κB p65), tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and myeloperoxidase (MPO)], ER stress [78-kDa glucose-regulated protein (GRP78), activating transcription factor 6 (ATF6) and CCAAT-enhancer-binding protein homologous protein (CHOP)] and apoptosis (caspase-3) markers in testicular tissues were determined using commercial enzyme-linked immunosorbent assay (ELISA) kits. Johnsen's testicle scoring system was used for histological evaluation. In the T/D group, it was determined that statistically significant increasing in the levels of oxidative stress, inflammation, ER stress and apoptosis compared with sham control group (p < 0.05). ARB administrations statistically significantly restored testicular I/R damage in a dose dependent manner (p < 0.05). In addition, it was determined that the data of histological examinations supported the biochemical results. Our findings support the hypothesis that ARB may be used as a protective agent against T/D-induced testicular damage.

Syringic acid ameliorates ischemia/reperfusion-induced testicular injury in rats via suppressing of HMGB1/NF-κB axis and endoplasmic reticulum stress.

PURPOSE: To investigate the possible protective role of syringic acid on torsion/detorsion-induced testicular injury using biochemical and histopathological approaches for the first time. METHODS: A total of 24 rats were divided into 4 groups: sham control, torsion/detorsion, torsion/detorsion + syringic acid (50 mg/kg and 100 mg/kg). Tissue malondialdehyde, total oxidant status and total antioxidant status levels were determined using colorimetric methods. Tissue 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, catalase, high mobility group box 1, nuclear factor kappa B protein 65, tumor necrosis factor-alpha, interleukin-6, myeloperoxidase, 78-kDa glucose-regulated protein, activating transcription factor-6, C/EBP homologous protein and caspase-3 levels were determined using commercial enzyme-linked immunosorbent assay kits. Johnsen's testicle scoring system was used for histological evaluation. RESULTS: Compared with the control group, the levels of oxidative stress, inflammation, endoplasmic reticulum stress and apoptosis were significantly increased in the torsion/detorsion group (p < 0.05). Syringic acid administrations statistically significantly restored these damage in a dose dependent manner (p < 0.05). Moreover, it was found that the results of histological examinations supported the biochemical results to a statistically significant extent. CONCLUSION: The overall results suggest that syringic acid emerges as a potential compound for the treatment of testicular torsion and may be subject to clinical trials.

Cytotoxic Activity and Docking Studies of 2-arenoxybenzaldehyde N-acyl Hydrazone and 1,3,4-Oxadiazole Derivatives against Various Cancer Cell Lines.

To understand whether previously synthesized novel hydrazone and oxadiazole derivatives have promising anticancer effects, docking studies and in vitro toxicity assays were performed on A-549, MDA-MB-231, and PC-3 cell lines. The antiproliferative properties of the compounds were investigated using molecular docking experiments. Each compound's best-docked poses, binding affinity, and receptor-ligand interaction were evaluated. Compounds' molecular weights, logPs, TPSAs, abilities to pass the blood-brain barrier, GI absorption qualities, and CYPP450 inhibition have been given. When the activities of these molecules were examined in vitro, for the A-549 cell line, hydrazone 1e had the minimum IC50 value of 13.39 µM. For the MDA-MB-231 cell line, oxadiazole 2l demonstrated the lowest IC50 value, with 22.73 µM. For PC-3, hydrazone 1d showed the lowest C50 value of 9.38 µM. The three most promising compounds were determined as compounds 1e, 1d, and 2a based on their minimum IC50 values, and an additional scratch assay was performed for A-549 and MDA-MB-231 cells, which have high migration capacity, for the three most potent molecules; it was determined that these molecules did not show a significant antimetastatic effect.

p-Coumaric acid alleviates cisplatin-induced ovarian toxicity in rats.

OBJECTIVE: The therapeutic value of cisplatin (CDDP) as an anticancer drug is limited by its ovo-otoxicity. The effect of natural phenolic acids in the prevention of many diseases related to oxidative stress has been reported. Here, the ability of p-coumaric (pCA) acid, a member of phenolic acids, to protect rat ovary tissue against CDDP-induced oxidative stress was investigated. METHODS: The study was carried out in five main groups containing six rats in each group: control, pCA (4 mg/kg), CDDP, CDDP plus pCA (2 mg/kg), and CDDP plus pCA (4 mg/kg). The levels of ovarian malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), catalase (CAT), 8-hydroxy-2'-deoxyguanosine (8-OHdG), caspase-3, and tumor necrosis factor-alpha (TNF-α) were determined. Hematoxylin and eosin staining method was employed for the histopathological examination. RESULTS: In the CDDP group, it is determined that statistically significant decreasing in the levels of TAS and CAT, and increasing in the levels of MDA, TOS, OSI, 8-OHdG, caspase-3, and TNF-α compared with control group (p < 0.05). pCA administration statistically significantly restored this damage in a dose-dependent manner (p < 0.05). Although vascular congestion, edema, hemorrhage, follicular degeneration, and leukocyte infiltration were significantly higher in the CDDP group than in the control group, pCA administrations statistically significantly restored these damages (p < 0.05). CONCLUSIONS: The data presented here indicate that pCA protects ovarian tissues of rats against CDDP-induced oxidative stress, inflammation, and apoptosis. It may be worthy to consider the usefulness of pCA as adjuvant therapy in cancer management.

Transition-metal-free intramolecular Friedel-Crafts reaction by alkene activation: A method for the synthesis of some novel xanthene derivatives.

In this work, new derivatives (substituted 9-methyl-9-arylxanthenes) of xanthene compounds (5a-l) of possible biological significance were synthesized by developing a new synthesis method. In order to obtain xanthene derivatives, the original alkene compounds to be used as the starting materials were synthesized in four steps using appropriate reactions. A cyclization reaction by intramolecular Friedel-Crafts alkylation was carried out in order to synthesize the desired xanthene derivatives using the alkenes as starting compounds. The intramolecular Friedel-Crafts reaction was catalyzed by trifluoroacetic acid (TFA) and provided some novel substituted 9-methyl-9-arylxanthenes with good yields at room temperature within 6-24 hours. As a result, an alkene compound was used for activation with TFA in the synthesis of xanthene through intramolecular Friedel-Crafts alkylation for the first time.

A rare vascular tumor of the spleen: Littoral cell angioma.

INTRODUCTION: Being a rare benign vascular tumor of the spleen, Littoral cell angioma involves multiple focal nodules in the spleen and splenectomy is used for both definitive diagnosis and treatment. PATIENTS AND METHODS: A 30-year-old male patient presented to our clinic with the complaints of intermittent abdominal pain and fever. In physical examination, splenomegaly was found and he was further evaluated with ultrasonography, tomography and magnetic resonance imaging that have revealed multiple solid mass lesions of various sizes in his spleen. The patient was administered open splenectomy and recovered uneventful. RESULTS: After histopathological and immunohistochemical analyses of the splenectomy material, he was diagnosed with Littoral cell angioma. CONCLUSIONS: For a timely diagnosis, Littoral cell angioma should be considered among the initial diagnoses in patients who were found to have splenomegaly in their physical examination and multiple masses in the spleen in radiological tests.

Effects of butein on renal ischemia/reperfusion injury: An experimental study.

OBJECTIVES: Renal ischemia/reperfusion (I/R) injury is a common cause of acute kidney injury. The aim of this study was to investigate the effect of butein on renal I/R injury. MATERIALS AND METHODS: Twenty-seven rats were randomly allocated to three groups (n = 9): a sham group, a renal I/Runtreated (control) group, and a renal I/R-butein group. The sham group underwent only opening and closing of the peritoneum. In the control group, an experimental I/R model was created and 1 cc isotonic saline was applied to the peritoneum. In the butein group, the experimental I/R model was created and 1 mg/kg butein was administered intraperitoneally 15 minutes before the beginning of ischemia. The left kidneys of the rats were histopathologically examined for tissue damage caused by I/R. RESULTS: Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. By contrast, 2 in the control group (22.2%) had small focal damaged areas, 1 (11.1%) had < 10% cortical damage, 5 (55.6%) had 10-25% cortical damage, and 1 (11.1%) had 25-75% cortical damage. The butein group had 1 (11.1%) normal kidney, 2 (22.2%) with small focal damaged areas, 4 (44.4%) with < 10% cortical damage, and 2 (22.2%) with 10-25% cortical damage. Tissue damage was significantly lower in the sham group than in the control and butein groups (p < 0.01). No statistically significant differences were observed in the histopathology of the control and butein groups (p > 0.05). CONCLUSIONS: Intraperitoneal administration of butein had no significant effect on renal tissue injury.

Protective effect of cordycepin on experimental renal ischemia/reperfusion injury in rats.

AIM: To date, various molecules have been investigated to reduce the effect of renal ischemia/reperfusion (I/R) injury. However, none have yet led to clinical use. The present study aimed to investigate the protective effect of cordycepin (C) on renal I/R injury in an experimental rat model. MATERIALS AND METHODS: Twenty-four mature Sprague Dawley female rat was randomly divided into three groups: Sham, I/R, I/R+C. All animals underwent abdominal exploration. To induce I/R injury, an atraumatic vascular bulldog clamp was applied to the right renal pedicle for 60 minutes (ischemia) and later clamp was removed to allow reperfusion in all rats, except for the sham group. In the I/R + C group, 10 mg/kg C was administered intraperitoneally, immediately after reperfusion. After 4 hours of reperfusion, the experiment was terminated with right nephrectomy. Histological studies and biochemical analyses were performed on the right nephrectomy specimens. EGTI (endothelial, glomerular, tubulointerstitial) histopathology scoring and semi-quantitative analysis of renal cortical necrosis were used for histological analyses and superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), total oxidant status (TOS) for biochemical analyses. RESULTS: Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. The I/R group had higher histopathological scores than the I/R + C group. In the biochemical analysis of the tissues, SOD, MDA, TOS values were found to be statistically different in the I/R group compared to the I/R + C group (p: 0.004, 0.004, 0.001 respectively). CONCLUSIONS: Intraperitoneal cordycepin injection following ischemia preserve renal tissue against oxidative stress in a rat model of renal I/R injury.

Protective effect of chlorogenic acid on renal ischemia/reperfusion injury in rats.

OBJECTIVES: Ischemia/reperfusion (I/R) injury is a common cause of renal injury and to date, many pharmacological agents have been identified to decrease I/R injury. One of the potential compound that can target I/R injury is chlorogenic acid (CGA). It has potent antiinflammatory, antibacterial, anti-oxidant, analgesic and antipyretic activities in in vitro experiments and in vivo animal models. The aim of the study was to investigate the protective characteristic of CGA on renal I/R injury. MATERIAL AND METHODS: 24 rats were randomly allocated to three groups (n = 8): Sham, I/R+CGA and I/R groups. CGA was administered intraperitoneally at a dose of 20 mg/kg, 10 min before reperfusion. I/R injury was achieved by clamping the left renal artery for 45 minutes, followed by reperfusion for 4 hours. The left kidneys of the rats were examined for tissue damage by histopathological and biochemical examination. For histological evaluation, EGTI scoring system was used. For biochemical examination total oxidant status, total antioxidant status and oxidative stress index were used. The power analysis indicated that 8 subjects per group would be required to produce 80% chance of achieving statistical significance at p < 0.05 level. The results are expressed as mean ± SD. Mann- Whitney U was performed for statistical analysis. RESULTS: Histopathological examination of the tissue damage revealed that all kidneys in the sham group were normal. I-R group had significantly higher histopathological scores than other groups. Histopathological improvement was seen after CGA treatment. TAS, TOS and OSI values of I-R group were significantly higher than sham group (0.88 vs 0.76 (p: 0.004), 13.8 vs 7.04 (p: 0.021) and 0.15 vs 0.09 (p: 0.034), respectively). In CGA treated group TAS, TOS and OSI levels were 0.84, 6.47 and 0.07, respectively. CGA treatment resulted in significant improvement in TOS and OSI parameters. CONCLUSIONS: CGA treatment provided marked improvement in renal histology and suppressed oxidative stress. Thus, CGA may have a protective effect in renal tissue against I/R injury.

Design and synthesis of novel cylopentapyrazoles bearing 1,2,3-thiadiazole moiety as potent antifungal agents.

In drug-resistant phytopathogenic fungi, there has been extensive research on microbiological and antifungal drug development. In this study, a novel series of cylopentapyrazole bearing a 1,2,3-thiadiazole ring 2a-e were designed and synthesized according to the principle of combination of bioactive structures. Thus, we have employed a [3 + 2] cycloaddition with 4-methyl-[1,2,3] thiadiazole-5-carboxylic acid hydrazones 1a-e and cyclopentadiene ring. Novel synthesized compounds were identified with IR, 1H and 13C NMR, mass spectrometry and elemental analysis then, antifungal activities were assayed. Based on our study, a combination of the compounds 1a and 2b possess remarkable antifungal activity against Botrytis cinerea AHU 9424 with 100% inhibition. EC50 values were calculated by studying different doses in combinations with high inhibition rates. The combination of 1a + 2b has an EC50 value at 6.37 and 13.85 µg/ml concentrations against B. cinerea and F. culmorum, respectively. The combination of compound 1a + 2b, having a cylopentapyrazole ring on the 1,2,3-thiadiazole backbone, shows promising fungicidal activity and deserves further development. Additionally, the homology model of the CYP51 enzyme that belongs toFusarium moniliformewas generated using CYP51B (PDB ID: 6CR2), and molecular docking was performed using this homology model for each compound. The results of this study clearly indicate that these novel compounds can be identified as promising lead compounds and potential fungicidal agents in future.

A Rare Cause of Abdominal Pain: Scar Endometriosis.

INTRODUCTION: Scar endometriosis (SE) is a rare pathology that develops in the scar tissue formed on the anterior abdominal wall usually after a cesarean section. There have been instances of women presenting to emergency or general surgery clinics with abdominal pain due to SE. MATERIALS AND METHODS: This study retrospectively reviews 19 patients who were operated on in our clinic between January 2010 and January 2017 with a prediagnosis of SE and were reported to have SE based on their pathology results. RESULTS: The mean age of the patients was 30.8 years (range: 20-49 years). The body mass indexes of 12 (63.2%) patients were ≥ 25. All patients had a history of cesarean section and 9 (47.4%) patients had undergone cesarean section once. With the exception of one patient who had her SE localized in her inguinal region, all patients had a mass localized on their anterior abdominal wall neighboring the incision and complained about cyclic pain starting in their premenstrual periods. The complaints began 2 years after their cesarean section in 10 (52.6%) patients. Mostly abdominal ultrasonography was used for diagnostic purposes. The lesions were totally excised and the SE diagnosis was made through a histopathological examination in all patients. No postoperative complications or recurrences were seen in any of the patients. CONCLUSION: Suspicion of SE is essential in women of reproductive age who have a history of cesarean section and complaints of an anterior abdominal wall mass and a pain at the scar site that is associated with their menstrual cycle. An accurate and early diagnosis can be established in such patients through a careful history and a good physical examination and possible morbidities can be prevented with an appropriate surgical intervention.

Synthesis and elastase inhibition activities of novel aryl, substituted aryl, and heteroaryl oxime ester derivatives.

Fifteen novel aryl, substituted aryl and heteroaryl γ-hydroxy- (2a-e), γ-methoxyimino- (3a-e), and γ-benzyloxyimino- (4a-e) butyric acid methyl esters were investigated for their enzyme inhibition, and the synthesis of 10 compounds (3a-e, 4a-e) is given in this study. The other five compounds (2a-e) were synthesized before in another study. Compounds 3a-e and 4a-e were synthesized in this work as original compounds and characterized by 1 H and 13 C NMR, IR, mass, and elemental analyses. Their (E/Z)-isomerisation ratios were analyzed by 1 H and 13 C NMR. All of them are of pure (E)-configuration. Due to the literature survey, the elastase inhibition activity was not studied for these compounds. Elastase inhibition ability was investigated in this work for five γ-hydroxy- (2a-e), five γ-methoxy- (3a-e), and five γ-benzyloxyimino- (4a-e) butyric acid methyl esters. All these 15 compounds showed elastase inhibition activity. Compound 2b was the best one and exhibited a better activity than the standard ursolic acid whereas compound 2a worked like the standard. All these compounds can be novel elastase inhibitor agents in the pharmaceutical and cosmetic industries.

Mechanism and selectivity of N-triflylphosphoramide catalyzed (3(+) + 2) cycloaddition between hydrazones and alkenes.

Brønsted acid catalyzed (3(+) + 2) cycloadditions between hydrazones and alkenes provide a general approach to pyrazolidines. The acidity of the Brønsted acid is crucial for the catalytic efficiency: the less acidic phosphoric acids are ineffective, while highly acidic chiral N-triflylphosphoramides are very efficient and can promote highly enantioselective cycloadditions. The mechanism and origins of catalytic efficiencies and selectivities of these reactions have been explored with density functional theory (M06-2X) calculations. Protonation of hydrazones by N-triflylphosphoramide produces hydrazonium-phosphoramide anion complexes. These ion-pair complexes are very reactive in (3(+) + 2) cycloadditions with alkenes, producing pyrazolidine products. Alternative 1,3-dipolar (3 + 2) cycloadditions with the analogous azomethine imines are much less favorable due to the endergonic isomerization of hydrazone to azomethine imine. With N-triflylphosphoramide catalyst, only a small distortion of the ion-pair complex is required to achieve its geometry in the (3(+) + 2) cycloaddition transition state. In contrast, the weak phosphoric acid does not protonate the hydrazone, and only a hydrogen-bonded complex is formed. Larger distortion energy is required for the hydrogen-bonded complex to achieve the "ion-pair" geometry in the cycloaddition transition state, and a significant barrier is found. On the basis of this mechanism, we have explained the origins of enantioselectivities when a chiral N-triflylphosphoramide catalyst is employed. We also report the experimental studies that extend the substrate scope of alkenes to ethyl vinyl ethers and thioethers.