@article {48761,
	title = {Identification of new modulator of DNA repairing pathways based on natural product ({\textpm})-peharmaline A},
	journal = {Bioorganic \& Medicinal Chemistry},
	volume = {91},
	year = {2023},
	month = {AUG},
	pages = {117365},
	type = {Article},
	abstract = {<p>
	The complex heterogenic environment of tumour mass often leads to drug resistance and facilitate chemo insensitivity triggering more malignant phenotypes among cancer patients. Major DNA-damaging cancer drugs have been consistently proven unsuccessful in terms of elevating chemo-resistance. (\&amp; PLUSMN;)-peharmaline A, a hybrid natural product isolated from seeds of Peganum harmala L. possesses significant cytotoxic activities. Herein, we have described the design, and synthesis of a novel library of close and simplified analogues around the anticancer natural product (\&amp; PLUSMN;)-peharmaline A and investigated their cytotoxic activities, which led to the identification of three structurally simplified lead compounds exhibiting better potency than parent natural product. Among them, demethoxy analogue of peharmaline A was further investigated for its anticancer potential eliciting demethoxy analogue as potent DNA-damage inducing agent attenuating the expression of the proteins responsible for the DNA damage repair. Therefore, this demethoxy analogue warrants detailed investigations for the confirmations of the molecular mechanism-based studies responsible for its anticancer activity.</p>
},
	keywords = {DNA damage, EMT, Pictet, Spengler reaction, Structure-activity relationship, Total synthesis},
	issn = {0968-0896},
	doi = {10.1016/j.bmc.2023.117365},
	author = {Kulkarni, Akshay S. and Dash, Anshurekha and Shingare, Rahul D. and Chand, Jagdish and Manhas, Diksha and Singh, Aman and Nandi, Utpal and Goswami, Anindya and Reddy, D. Srinivasa}
}
