Dataset Information

Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic/toxicity prediction and anti-tumor activity in vitro.

ABSTRACT: Despite the development of temozolomide (TMZ), a novel type of glioma therapeutic drug, malignant glioma remains to cause severe damage to human health. The present study aimed to utilize the molecular biological differences between tumor and normal cells to design TMZ derivatives with improved selectivity and targeting using computer-aided drug design (CADD). Taking alkylglycerone phosphate synthase (AGPS) as a target, a 3D structure-activity relationship model was built using CADD technology; molecular docking of isothiocyanate (ITC) and TMZ compounds was conducted; ITC-TMZ derivatives were designed; and predictions on the absorption, distribution, metabolism and excretion (ADME) processes and toxicity of the ITC-TMZ derivatives were established in order to obtain improved understanding of the structure-activity relationship of the candidate compounds. Using these techniques, it was identified that the docking scores of the structural derivatives S1-9 were higher than that of TMZ. Additionally, S3, -6, -7, -8, -9 and -10 exhibited enhanced ADME and similar toxicity to that of TMZ. The half maximal inhibitory concentrations of the CADD derivatives were also assessed in the glioma U87MG and U251 cell lines, and the activities of S1, -3, -8 and -10 were determined to be greater than that of TMZ, suggesting their potential as anti-cancer drugs with adequate AGPS targeting, ADME/toxicity and anti-tumor activity.

SUBMITTER: Yang B

PROVIDER: S-EPMC5867473 | biostudies-literature | 2018 Mar

REPOSITORIES: biostudies-literature

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Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic/toxicity prediction and anti-tumor activity <i>in vitro</i>.

Yang Bing B Li Xiaobo X He Lu L Zhu Yu Y

Biomedical reports 20180131 3

Despite the development of temozolomide (TMZ), a novel type of glioma therapeutic drug, malignant glioma remains to cause severe damage to human health. The present study aimed to utilize the molecular biological differences between tumor and normal cells to design TMZ derivatives with improved selectivity and targeting using computer-aided drug design (CADD). Taking alkylglycerone phosphate synthase (AGPS) as a target, a 3D structure-activity relationship model was built using CADD technology; ...[more]

PMID: 29599977

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Project description:Recent data indicates limited awareness and compliance on infection prevention procedures by dental offices and by dental laboratories. Guidelines for infection prevention in dentistry have been published by Centres for Disease Control and Prevention since 2003; the section "IX-Special consideration" includes a subsection concerning the prevention in dental laboratories, but it has not been modernised in later versions to fit the needs of traditional and computer-aided technology. Traditional techniques required disinfecting items (impression, chewing waxes, and appliances) with well-suited products, which are also chosen for limiting impression changes or appliance deterioration. Effective procedures are available with difficulties. Some of these contain irritant or non-eco-friendly disinfectants. The transport of impression, to dental laboratories, is often delayed with limited precautions for limiting cross-infection. Gypsum casts are frequently contaminated mainly by bacteria and their antibiotic-resistant strains and even stored for long periods during dental implant supported restoration and orthodontic therapy, becoming a hidden source of infection. Nowadays, computer-aided design/computer-aided manufacturing technology seems to be an interesting way to promote both business and safety, being more comfortable for patients and more accurate than traditional technology. A further advantage is easier infection prevention since, for the most part, mainly digital impression and casts are not a source of cross-infection and the transport of contaminated items is reduced and limited to try-in stages. Nevertheless, a peculiar feature is that a digital electronic file is of course unalterable, but may be ruined by a computer virus. Additionally, the reconditioning of scanner tips is determinant for the optical characteristics and long term use of the scanner, but information for its reconditioning from producers is often limited. This study focuses on some critical points including (a) insufficient guidelines, (b) choice of proper procedure for scanner reconditioning, and (c) data protection in relation to patient privacy.

Dataset Information

Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic/toxicity prediction and anti-tumor activity in vitro.

Publications

Computer-aided design of temozolomide derivatives based on alkylglycerone phosphate synthase structure with isothiocyanate and their pharmacokinetic/toxicity prediction and anti-tumor activity <i>in vitro</i>.

Similar Datasets

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