Nostocine A Derivatives as Human DNA Topoisomerase II-alpha Inhibitor

Abstract

Introduction: Due to heavy morbidity and mortality from cancer, the designing of newer drugable molecules against breast cancer is the call of day. As, Schiff-base sulfonamides have been widely used in tumor treatments. Methods: Nostocine-sulfonamide (NS) Schiff-base molecules were designed with tools of bioinformatics against the target enzyme, human topoisomerase II-alpha (topo IIa) against breast cancer. The designed NS conjugates were assessed by RO5, ADMET and molecular docking. Results: Herein, these analogues, NS-20b (Nostocine A-sulfaphenazole), 12a (Nostocine A-sulfisoxazole) and 16b (Nostocine A-sulfamethazineare) are N-heteroaryl substituted sulfonamide moieties linked with pyrazolo[4,3-e][1,2,4]triazine of Nostocine A. Conclusion: These derivatives would act as potent inhibitors of topo IIa for breast cancer.

New 2H‐Chromene‐Based Hydrazone Derivatives as Promising Anti‐Breast Cancer Agents: Efficient Synthesis, Spectral Characterization, Molecular Docking, and ADMET Studies

“…According to "Lipinski's Rule of five (RO5)" a compound may be considered an orally active drug if it would not violate more than one of five guidelines: Molecular Weight (MW) should be � 500 g/mol, octanol-water partition coefficient (cLog P) should be � 5, Number of hydrogen bond acceptors (H-ba) should be � 10, number of hydrogen bond donors (H-bd) should be � 5 and tropological polar surface area (tPSA) should be � 150 Å 2 . [72][73][74] The obtained predictions revealed the physicochemical properties were within the limit. The drug-likeness requirements are not violated by the topological polar surface area (tPSA) of the compounds.…”

“…The Lipinski's, Ghose's, and Veber's parameter results of tested compounds 10 r , 12 b , and a standard drug (Doxorubicin) are presented in table 7. According to “Lipinski's Rule of five (RO5)” a compound may be considered an orally active drug if it would not violate more than one of five guidelines: Molecular Weight (MW) should be ≤500 g/mol, octanol‐water partition coefficient (cLog P) should be ≤5, Number of hydrogen bond acceptors (H‐ba) should be ≤ 10, number of hydrogen bond donors (H‐bd) should be ≤5 and tropological polar surface area (tPSA) should be ≤150 Å 2 [72–74] . The obtained predictions revealed the physicochemical properties were within the limit.…”

“…Starting reagents, salicylaldehydes, cinnamaldehyde, pyrrolidine, K 2 CO 3 , DABCO, phenyl hydrazine, 4‐(Trifluoromethyl)phenylhydrazine, isatin, and hydrazine hydrate were purchased from Sigma‐Aldrich chemical company and utilized without any additional purification. Following the steps outlined in the described protocols, [18,19,71,72] the compounds 8 a – w were successfully synthesized. The reaction progress was tracked using silica gel 60 F254‐coated TLC plates (Merck KGaA, Darmstadt, Germany), and visualized by Short‐UV light at 254 nm.…”

Structure-Based In Silico Investigation of Agonists for Proteins Involved in Breast Cancer

“…The SwissADME tool [ 30 ] by ExPASy tools was used to determine the values of parameters proposed in the Lipinski Rule of Five [ 31 ]. In addition to lipophilicity, the number of hydrogen bond donors and accepters, and molecular weight, one parameter, molar refractivity (Ghose rule), was also taken into account to test the drug-likeliness of all the 62 compounds [ 32 ].…”