In Silico Screening Studies on Methanesulfonamide Derivatives as Dual Hsp27 and Tubulin Inhibitors Using QSAR and Molecular Docking
Message:
Article Type:
Research/Original Article (دارای رتبه معتبر)
Abstract:
The expression of heat shock protein 27 (Hsp27) as a chaperone protein, is increased in response to various stress stimuli such as anticancer chemotherapy. This phenomenon can lead to survive of the cells and causes drug resistance. In this study, a series of methanesulfonamide derivatives as dual Hsp27 and tubulin inhibitors in the treatment of cancer were applied to quantitative structure–activity relationship (QSAR) analysis. A collection of chemometrics methods such as MLR, FA-MLR, PCR, and GA-PLS was applied to make relations between structural characteristics and anti-proliferative activity of them against SKBR-3 breast cancer cell line. The best multiple linear regression equation was obtained from GA-PLS. Concerning this model, new potent lead compounds were designed based on new structural patterns using in silico-screening study. To obtain their binding mode, binding site and types of their interactions to both tubulin and HSP27, molecular docking studies were also conducted on these compounds. The validity of docking protocol was also explored. The results obtained from this docking study indicate that the important amino acids inside the active site cavity that are in charge of essential interactions with HSP27 are Arg140, Thr139, Phe138, Cys137, Arg136, Phe104, His103, Val101, and Asp100. And this important amino acids in essential interactions with tubulin are Asn258, Val238, Cys241, Asn350, Leu255, Met259, Val315, Thr353, Arg221, Thr179 and Ser178.
Language:
English
Published:
Journal of Sciences, Islamic Republic of Iran, Volume:29 Issue: 3, Summer 2018
Pages:
221 to 240
magiran.com/p1873935  
دانلود و مطالعه متن این مقاله با یکی از روشهای زیر امکان پذیر است:
اشتراک شخصی
با عضویت و پرداخت آنلاین حق اشتراک یک‌ساله به مبلغ 990,000ريال می‌توانید 70 عنوان مطلب دانلود کنید!
اشتراک سازمانی
به کتابخانه دانشگاه یا محل کار خود پیشنهاد کنید تا اشتراک سازمانی این پایگاه را برای دسترسی نامحدود همه کاربران به متن مطالب تهیه نمایند!
توجه!
  • حق عضویت دریافتی صرف حمایت از نشریات عضو و نگهداری، تکمیل و توسعه مگیران می‌شود.
  • پرداخت حق اشتراک و دانلود مقالات اجازه بازنشر آن در سایر رسانه‌های چاپی و دیجیتال را به کاربر نمی‌دهد.
دسترسی سراسری کاربران دانشگاه پیام نور!
اعضای هیئت علمی و دانشجویان دانشگاه پیام نور در سراسر کشور، در صورت ثبت نام با ایمیل دانشگاهی، تا پایان فروردین ماه 1403 به مقالات سایت دسترسی خواهند داشت!
In order to view content subscription is required

Personal subscription
Subscribe magiran.com for 50 € euros via PayPal and download 70 articles during a year.
Organization subscription
Please contact us to subscribe your university or library for unlimited access!