title: Virtual Screening Approaches in Identification of Bioactive Compounds Akin to Delphinidin as Potential HER2 Inhibitors for the Treatment of Breast Cancer.
abstract: Small molecule tyrosine kinase inhibitors targeting HER 2 receptors have emerged as an important therapeutic approach in inhibition of downstream proliferation and survival signals for the treatment of breast cancers. Recent drug discovery efforts have demonstrated that naturally occurring polyphenolic compounds like delphinidin have potential to inhibit proliferation and promote apoptosis of breast cancer cells by targeting HER2 receptors. While delphinidin may thus reduce tumour size, it is associated with serious side effects like dysphonia. Owing to the narrow therapeutic window of delphinidin, the present study aimed to identify high affinity compounds targeting HER2 with safer pharmacological profiles than delphinidin through virtual screening approaches. Delphinidin served as the query parent for identification of structurally similar compounds by Tanimoto-based similarity searching with a threshold of 95% against the PubChem database. The compounds retrieved were further subjected to Lipinski and Verber's filters to obtain drug like agents, then further filtered by diversity based screens with a cut off of 0.6. The compound with Pubchem ID: 91596862 was identified to have higher affinity than its parent. In addition it also proved to be non-toxic with a better ADMET profile and higher kinase activity. The compound identified in the study can be put to further in vitro drug testing to complement the present study.
authors.affiliation: In silico Research Laboratory, Eminent Biosciences Vijaynagar, Indore, Madhya Pradesh, India E-mail : skysanjeev@gmail.com.
authors.forename: Kavisha
authors.initials: K
authors.lastname: Patidar
authors.forename: Aruna
authors.initials: A
authors.lastname: Deshmukh
authors.forename: Srinivas
authors.initials: S
authors.lastname: Bandaru
authors.forename: Chandana
authors.initials: C
authors.lastname: Lakkaraju
authors.forename: Amandeep
authors.initials: A
authors.lastname: Girdhar
authors.forename: Gutlapalli
authors.initials: G
authors.lastname: Vr
authors.forename: Tushar
authors.initials: T
authors.lastname: Banerjee
authors.forename: Anuraj
authors.initials: A
authors.lastname: Nayarisseri
authors.forename: Sanjeev Kumar
authors.initials: SK
authors.lastname: Singh
mesh_terms: D000872:Anthocyanins / Q000737:chemistry* / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D062126:Databases, Chemical; D055808:Drug Discovery; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
chemical_list: D000872:Anthocyanins; D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human; C017185:delphinidin