Indole hybridized diazenyl derivatives: synthesis, antimicrobial activity, cytotoxicity evaluation and docking studies

• Published in: BMC chemistry 2019-05, Vol.13 (1), p.65-18, Article 65
• Main Authors: Kaur, Harmeet, Singh, Jasbir, Narasimhan, Balasubramanian
• Format: Article
• Language: English
• Subjects: Amines; Antiinfectives and antibacterials; Antimicrobial; Antimicrobial agents; Bacteria; Binding sites; Breast cancer; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Colon; Cytotoxicity; Derivatives; Diazenyl; Dilution; Docking; Doxorubicin; E coli; Fungi; Gram-negative bacteria; Indole; Medicinal Chemistry; Molecular interactions; Research Article; Toxicity
• ISSN: 2661-801X; 2661-801X
• DOI: 10.1186/s13065-019-0580-0

Background In search of effective antimicrobial and cytotoxic agents, a series of indole hybridized diazenyl derivatives ( DS-1 to DS-21 ) was efficiently prepared by condensation of diazotized p -aminoacetophenone with indole or nitroindole followed by reaction with different aromatic/heteroaromatic amines of biological significance. The synthesized derivatives were characterized by various spectroscopic techniques. Methodology The antimicrobial evaluation of DS-1 to DS-23 was done by tube dilution method against various pathogenic bacterial and fungal strains. The active antimicrobial derivatives were further evaluated for cytotoxicity against human lung carcinoma cell line (HCT-116), breast cancer cell line (MDAMB231), leukemic cancer cell line (K562), and normal cell line (HEK293) by MTT assay using doxorubicin as the standard drug. The test derivatives were additionally docked for the B-subunit of enzyme DNA gyrase from E. coli at the ATPase binding site to study the molecular interactions using Schrodinger maestro v11.5 software. Results and discussion Most of the synthesized derivatives have shown high activity against Gram-negative bacteria particularly E. coli and K. pneumonia with MIC ranging from 1.95 to 7.81 μg/ml. The derivatives have demonstrated very less activity against tested Gram positive bacterial and fungal strains. The derivatives DS-14 and DS-20 have been found to active against breast cancer cell line and human colon carcinoma cell line having IC 50 in the range of 19–65 µg/ml. All the derivatives were found to less potent against leukemic cancer cell line. The synthesized derivatives have revealed their safety by exhibiting very less cytotoxicity against the normal cell line (HEK-293) with IC 50  > 100 µg/ml. Most of the active derivatives have shown good docking scores in comparison to the standard drugs against DNA gyrase from E. coli . Further ADME predictions by Qikprop module of the Schrodinger confirmed these molecules have drug like properties. Conclusion The derivatives DS-14 and DS-20 have shown potential against Gram-negative bacteria and breast cancer cell line and can be used as a lead for rational drug designing of the antimicrobial and cytotoxic agents. .