title: Sequential one-pot synthesis of bis(indolyl)glyoxylamides: Evaluation of antibacterial and anticancer activities.
abstract: A series of bis(indolyl)glyoxylamides 10a-n has been designed and synthesized. In situ generated indole-3-glyoxalylchloride from the reaction of readily available indole 9 with oxalyl chloride was treated with tryptamine to produce bis(indolyl)glyoxylamides 10a-n in 82-93% yields. All the synthesized bis(indolyl)glyoxylamides were well characterized and tested for their antibacterial activity against Gram-positive and Gram-negative bacterial strains. Compounds 10d, 10g and 10i were found to display potent antibacterial activity against Gram-negative strain. Further, the cytotoxicity of bis(indolyl)glyoxylamides 10a-n were evaluated against a panel of human cancer cell lines. Of the screened analogues, compound 10f (IC50=22.34μM; HeLa, 24.05μM; PC-3, 21.13μM; MDA-MB-231 and 29.94μM; BxPC-3) was identified as the most potent analogue of the series. Exposure of PC-3 cells to either 10a or 10f resulted in increased levels of cleaved PARP1, indicating that bis(indolyl)glyoxylamides induce apoptosis in PC-3 cells. Most importantly, compounds 10d, 10g and 10i were completely ineffective in mammalian cells, suggesting that they target bacterial-specific targets and thus will not display any toxicity in host cells.
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: Mukund P
authors.initials: MP
authors.lastname: Tantak
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: Vishakha
authors.initials: V
authors.lastname: Gupta
authors.affiliation: Department of Chemistry, Purdue University Center for Cancer Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA.
authors.forename: Kumar
authors.initials: K
authors.lastname: Nikhil
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India.
authors.forename: V
authors.initials: V
authors.lastname: Arun
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors.forename: Rajnish Prakash
authors.initials: RP
authors.lastname: Singh
authors.affiliation: Department of Biological Sciences, Birla Institute of Technology and Science, Pilani 333031, Rajasthan, India.
authors.forename: Prabhat Nath
authors.initials: PN
authors.lastname: Jha
authors.affiliation: Department of Chemistry, Purdue University Center for Cancer Research, Purdue University, 560 Oval Drive, West Lafayette, IN 47907, USA. Electronic address: shah23@purdue.edu.
authors.forename: Kavita
authors.initials: K
authors.lastname: Shah
authors.affiliation: Department of Chemistry, Birla Institute of Technology and Science, Pilani 333 031, India. Electronic address: dalipk@pilani.bits-pilani.ac.in.
authors.forename: Dalip
authors.initials: D
authors.lastname: Kumar
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D007211:Indoles; C000620937:bis(indolyl)glyoxylamide
keywords: Antibacterial; Apoptosis; Bisindoles; Cancer; Cytotoxicity; Glyoxylamides