Identification of promising inhibitors against breast cancer disease by targeting NUDIX hydrolase 5 (NUDT5) biomolecule

Abstract

It is well documented that NUDT5 enzyme inhibition in breast cancer cell lines arrest cancer cells growth, invasiveness and migration. The NUDT5 enzyme enhances breast cancer aggressiveness and act as key regulator of oncogenic pathways. Similarly, the NUDT5 enzyme plays a primer role in ATP-dependent cellular processes and proliferation in breast cancer. Thus, the NUDT5 enzyme plays a profound contribution in promoting breast cancers carcinogenesis and could be an ideal target for anti-cancer drug discovery. In this work, LAS_51382001, LAS_51177972 and LAS_51380924 with binding energy of −12.64 kcal/mol, −11.59 kcal/mol and −10.01 kcal/mol, respectively were filtered as lead molecules. The control molecule binding energy was −10.87 kcal/mol. The system dynamics were found uniform in molecular dynamics simulation studies and observed with no major structural changes. Among the leads, the LAS_51177972 showed the most stable binding energy values. The MM-GBSA binding energy of the compound was −37.07 kcal/mol and MM-PBSA binding energy of −43.56 kcal/mol. Similarly, the compound revealed very stable WaterSwap absolute binding energy values; Bennett’s, TI and FEP energy of −36.2 kcal/mol, −36.13 kcal/mol and −36.58 kcal/mol, respectively. Similarly, the leads reported very favorable physicochemical properties, water solubility, pharmacokinetics, druglikeness and medicinal chemistry properties. In a nutshell, the compounds are potent in term of the current computational study however, need to be subjected to experimental studies.Communicated by Ramaswamy H. Sarma