Synthesis, biological activity and molecular modeling studies on 1H-benzimidazole derivatives as acetylcholinesterase inhibitors

WOS: 000323294600007PubMed ID: 23891231A series of N-(2-[4-(1H-benzimidazole-2-yl)phenoxy]ethyl}substituted amine derivatives were designed to assess cholinesterase inhibitor activities. Acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitor activities were evaluated in vitro by using Ellman's method. It was discovered that most of the compounds displayed AChE and/or BuChE inhibitor activity and few compounds were selective against AChE/BuChE. Compound 3c and 3e were the most active compounds in the series against eeAChE and hAChE, respectively. Molecular docking studies and molecular dynamics simulations were also carried out. (C) 2013 Elsevier Ltd. All rights reserved

Multifunctional cholinesterase inhibitors for Alzheimer's disease: Synthesis, biological evaluations, and docking studies of o/p-propoxyphenylsubstituted-1H-benzimidazole derivatives

WOS: 000440404700001PubMed ID: 29984517This study indicates the synthesis, cholinesterase (ChE) inhibitory activity, and molecular modeling studies of 48 compounds as o- and p-(3-substitutedethoxyphenyl)-1H-benzimidazole derivatives. According to the ChE inhibitor activity results, generally, para series are more active against acetylcholinesterase (AChE) whereas ortho series are more active against butyrylcholinesterase (BuChE). The most active compounds against AChE and BuChE are compounds A12 and B14 with IC50 values of 0.14 and 0.22M, respectively. Additionally, the most active 16 compounds against AChE/BuChE were chosen to investigate the neuroprotective effects, and the results indicated that most of the compounds have free radical scavenging properties and show their effects by reducing free radical production; moreover, some of the compounds significantly increased the viability of SH-SY5Y cells exposed to H2O2. Overall, compounds A12 and B14 with potential AChE and BuChE inhibitory activities, high neuroprotection against H2O2-induced toxicity, free radical scavenging properties, and metal chelating abilities may be considered as lead molecules for the development of multi-target-directed ligands against Alzheimer's disease.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213S027]TUBITAK, Grant number: 213S02

Hybrid Arc Could Combine the Benefits of IMRT and VMAT to Deliver a Fast, Conformal, Homogeneous Treatment in Non-Small Cell Lung Cancer without Limitations of Low Dose Bath: A Planning Study

Intensity Modulated Radiotherapy (IMRT, step and shoot) is emerging as the standard of care in non-small cell lung cancer (NSCLC) patient treatments. Volumetric Arc Therapy (VMAT) delivered with two arcs offers fast and homogeneous dose delivery with known limitations of increased volumes of low dose. The aim of this study is to define whether Hybrid volumetric arc IMRT (HA-IMRT: IMRT and VMAT combination) offers a superior dose distribution over IMRT without the limitations found in VMAT delivery alone. Ten (previously 4DCT planned) locally advanced NSCLC patients treated by IMRT to 70 Gy in 35 fractions were retrospectively re-planned using the HA-IMRT technique. Respiratory correlated imaging (3 mm slice thickness) were generated utilizing the Philips Large Bore 16 slice CT Scanner (Phillips, Inc.). Treatment planning was performed using The Philips Pinnacle Treatment Planning System v. 9.0 (Philips Medical, Cleveland, OH). The PTV was defined as the Integrated Tumor Volume (ITV=internal GTV contoured on all respiratory data sets plus 8 mm margin for all histologies) with a 4 mm margin added. Lung parenchyme was defined and contoured using the 50% phase. Conventional IMRT plans used 6:8 non coplanar or coplanar fields and VMAT plans were generated using two 180 degrees arcs. HA-IMRT plans were generated using a combination of 60% conventional IMRT with 40% VMAT. The maximum dose (Gy) to the spinal cord, V5, V10, V20 for total lung, V20 and V30 for the ipsilateral lung, V30 for heart, V50 and V70 for esophagus, and the V77 for the Clinical Treat Volume (CTV) were compared for all techniques utilizing the Dose Volume Histograms. In addition, total monitor units (MU), total treatment time (I I) and the conformality index (CI) were compared.. Conventional IMRT delivers less low dose to the lung compared to VMAT alone. (V5 VMAT (V5: 55.0% vs 63.0%, p=0.005; V10: 41.4% vs 43.9%, p=0.018). However, VMAT is superior in total lung V20 (V20:30.6% vs 29.3% p=0.010), ipsilateral lung doses (V20:55.5% vs 52.8% p=0.008; V30: 46.1% vs 42.9% p= 0.012), and in heart sparing. (V30: 21.09% vs 17.78% p=0.015; MHD: 15.92% vs 14.81% p=0.021). It is also superior in conformality (CI 1.51 vs 1.26 p=0.005) and treatment delivery is faster ( 293 min vs 108 min p=0.005) with lower MUs (24805 vs 19141 p=0.005). HA-IMRT was found to be superior to VMAT in terms of total lung low dose volumes (V5:58.1% vs 63.0%, p=0.005; V10:42.2% vs 44.9%, p=0.027), superior to IMRT for ipsilateral lung doses (V20: 53.6% vs 55.5%, p=0.007; V30: 43.4% vs 46.1%, p=0.018), and superior in treatment time (199 min vs 293 min, p=0.005) with lower MU's (22155 vs 24805, p=.005). Overall, HA-IMRT provides a more homogenous dose distribution (CTV: V77: 0.55% vs 2.1% vs 1.7%, p=0.000) compared to IMRT and VMAT alone. All three plans provided comparable esophagus and spinal cord Organ at Risk (OAR) doses. HA-IMRT seems to combine the benefits of both conventional IMRT and VMAT; such as to deliver a faster, more conformal, homogeneous treatment in comparison to ssIMRT, and to deliver lower dose to lung in comparison to VMAT

1H-benzimidazole derivatives as butyrylcholinesterase inhibitors: synthesis and molecular modeling studies

WOS: 000385175500024A series of N-{2-[2-(1H-benzimidazole-2-yl)phenoxy]ethyl} substituted amine derivatives were synthesized and tested for their cholinesterase inhibitor activity. Acetylcholinesterase and butyrylcholinesterase inhibitor activities were evaluated in vitro by using Ellman's method. According to the activity results, all of the compounds displayed moderate acetylcholinesterase inhibitory activity and most of the compounds displayed remarkable butyrylcholinesterase inhibitory activity. Compound 3d was the most active compound in the series and also a selective butyrylcholinesterase inhibitor. Molecular docking studies and molecular dynamic simulations were also carried out.TUBITAK (Turkish Scientific and Technical Research Council)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [213S027]This study was partially supported by TUBITAK (Turkish Scientific and Technical Research Council) (Project number: 213S027). We appreciate the support of Professor Dr. Wolfgang Sippl for molecular modeling studies. We also thank the Medicinal Chemistry Department of Martin Luther University Institute of Pharmacy and also Pharmaceutical Sciences Research Centre (FABAL) of Ege University Faculty of Pharmacy for equipmental support

Current practices of craniospinal irradiation techniques in Turkey: a comprehensive dosimetric analysis

Objective: This study evaluates various craniospinal irradiation (CSI) techniques used in Turkish centers to understand their advantages, disadvantages and overall effectiveness, with a focus on enhancing dose distribution. Methods: Anonymized CT scans of adult and pediatric patients, alongside target volumes and organ-at-risk (OAR) structures, were shared with 25 local radiotherapy centers. They were tasked to develop optimal treatment plans delivering 36 Gy in 20 fractions with 95% PTV coverage, while minimizing OAR exposure. The same CT data was sent to a US proton therapy center for comparison. Various planning systems and treatment techniques (3D conformal RT, IMRT, VMAT, tomotherapy) were utilized. Elekta Proknow software was used to analyze parameters, assess dose distributions, mean doses, conformity index (CI), and homogeneity index (HI) for both target volumes and OARs. Comparisons were made against proton therapy. Results: All techniques consistently achieved excellent PTV coverage (V95 > 98%) for both adult and pediatric patients. Tomotherapy closely approached ideal Dmean doses for all PTVs, while 3D-CRT had higher Dmean for PTV_brain. Tomotherapy excelled in CI and HI for PTVs. IMRT resulted in lower pediatric heart, kidney, parotid, and eye doses, while 3D-CRT achieved the lowest adult lung doses. Tomotherapy approached proton therapy doses for adult kidneys and thyroid, while IMRT excelled for adult heart, kidney, parotid, esophagus, and eyes. Conclusion: Modern radiotherapy techniques offer improved target coverage and OAR protection. However, 3D techniques are continued to be used for CSI. Notably, proton therapy stands out as the most efficient approach, closely followed by Tomotherapy in terms of achieving superior target coverage and OAR protection