Presentation Title

In silico molecular docking and ADMET predictions of novel nucleoside analogues as potential anticancer drugs

Faculty Mentor

Ahmed Awad

Start Date

23-11-2019 10:00 AM

End Date

23-11-2019 10:45 AM

Location

245

Session

poster 3

Type of Presentation

Poster

Subject Area

physical_mathematical_sciences

Abstract

Clinically approved nucleoside analogues such as Gemcitabine, Clofarabine, Fludarabine, and Cladribine have been shown to inhibit enzymes associated with cancer. However, issues with toxicity and cancer resistance necessitate the development of new drugs. Therefore, six novel nucleoside analogue derivatives were designed to inhibit the activity of RNR, an enzyme that catalyzes the dihydroxylation of the ribose nucleotides, by binding in the catalytic site. An in silico molecular docking study was performed using Internal Coordinate Mechanics to predict the conformation and H-bonding formation of these compounds within one of the enzymes linked to cancer. Importantly, the addition of electron-withdrawing atoms fluorine and chlorine enhanced binding to the analogues, whereas the addition of electron-donating groups to the ring diminished binding. The analogues containing the electron withdrawing groups adapted a “U” conformation , which may contribute to its binding strength to the enzyme. Moreover, an in silico Admisnitration, Distribution, Metabolism, Excretion, Toxicity (ADMET) study of the analogues was performed using the admetSAR and SwissADME software platforms. The results from applying this software to the current system seemed to confirm that the lead compounds have favorable pharmacokinetic and toxicity profiles. Additionally, the compounds are hypothesized to be soluble, non-AMES toxic and non-carcinogenic. The findings of this investigation support the development of nucleoside analogues, enhanced with electron-withdrawing atoms, as a promising new class of cancer inhibitor drugs.

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Nov 23rd, 10:00 AM Nov 23rd, 10:45 AM

In silico molecular docking and ADMET predictions of novel nucleoside analogues as potential anticancer drugs

245

Clinically approved nucleoside analogues such as Gemcitabine, Clofarabine, Fludarabine, and Cladribine have been shown to inhibit enzymes associated with cancer. However, issues with toxicity and cancer resistance necessitate the development of new drugs. Therefore, six novel nucleoside analogue derivatives were designed to inhibit the activity of RNR, an enzyme that catalyzes the dihydroxylation of the ribose nucleotides, by binding in the catalytic site. An in silico molecular docking study was performed using Internal Coordinate Mechanics to predict the conformation and H-bonding formation of these compounds within one of the enzymes linked to cancer. Importantly, the addition of electron-withdrawing atoms fluorine and chlorine enhanced binding to the analogues, whereas the addition of electron-donating groups to the ring diminished binding. The analogues containing the electron withdrawing groups adapted a “U” conformation , which may contribute to its binding strength to the enzyme. Moreover, an in silico Admisnitration, Distribution, Metabolism, Excretion, Toxicity (ADMET) study of the analogues was performed using the admetSAR and SwissADME software platforms. The results from applying this software to the current system seemed to confirm that the lead compounds have favorable pharmacokinetic and toxicity profiles. Additionally, the compounds are hypothesized to be soluble, non-AMES toxic and non-carcinogenic. The findings of this investigation support the development of nucleoside analogues, enhanced with electron-withdrawing atoms, as a promising new class of cancer inhibitor drugs.