title: Design, synthesis, anticancer, antimicrobial activities and molecular docking studies of theophylline containing acetylenes and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives.
abstract: A new series of theophylline containing acetylene derivatives (6a-6b and 7-13) and theophylline containing 1,2,3-triazoles with variant nucleoside derivatives (20-32) have been designed and synthesized. These compounds were screened for anticancer and antimicrobial activity. Further the computational docking and 2D QSAR were performed using MOE software to identify novel scaffolds. The results showed that compound 29 and 30 exhibit significant cytotoxic effect on all four cancer cells such as lung (A549), colon (HT-29), breast (MCF-7) and melanoma (A375) with IC50 values of 2.56, 2.19, 1.89, 4.89 μM and 3.57, 2.90, 2.10, 5.81 μM respectively. Whereas quite different results were observed for these compounds in antimicrobial studies. Compounds 11, 21 and 26 have exhibited significant minimum inhibitory concentrations (MIC) against Staphylococcus aureus, Bacillus cereus, Escherichia coli and Pseudomonas aeruginosa. The docking studies demonstrate that compound 27, 28, 29 and 30 have good dock score and binding affinities with various therapeutic targets in cancer cell proliferation. In addition these compounds have shown acceptable correlation with bioassay results in the regression plots generated in 2D QSAR models. This is the first report to demonstrate the theophylline containing acetylene derivatives and theophylline containing 1,2,3-triazole nucleoside hybrids as potential anticancer and antimicrobial agents with comprehensive in silico analysis.
authors.affiliation: Dr.MACS Bio-PharmaPvt.Ltd, Factory, Plot-79/B&C, Pasamylaram, Patancheru, Medak (Dist), 502307, Telangana, India.
authors.forename: Radhakrishnam Raju
authors.initials: RR
authors.lastname: Ruddarraju
authors.affiliation: Dr.MACS Bio-PharmaPvt.Ltd, Factory, Plot-79/B&C, Pasamylaram, Patancheru, Medak (Dist), 502307, Telangana, India. Electronic address: drmacs36@gmail.com.
authors.forename: Adharvana Chari
authors.initials: AC
authors.lastname: Murugulla
authors.affiliation: Dr.MACS Bio-PharmaPvt.Ltd, Factory, Plot-79/B&C, Pasamylaram, Patancheru, Medak (Dist), 502307, Telangana, India.
authors.forename: Ravindar
authors.initials: R
authors.lastname: Kotla
authors.affiliation: Bioinformatics Center, Division of Molecular Biology, Department of Zoology, Sri Venkateswara University, Tirupati, 517 502, Andhra Pradesh, India.
authors.forename: Muni
authors.initials: M
authors.lastname: Chandra Babu Tirumalasetty
authors.affiliation: Bioinformatics Center, Division of Molecular Biology, Department of Zoology, Sri Venkateswara University, Tirupati, 517 502, Andhra Pradesh, India.
authors.forename: Rajendra
authors.initials: R
authors.lastname: Wudayagiri
authors.affiliation: Dr.MACS Bio-PharmaPvt.Ltd, Factory, Plot-79/B&C, Pasamylaram, Patancheru, Medak (Dist), 502307, Telangana, India.
authors.forename: Shobha
authors.initials: S
authors.lastname: Donthabakthuni
authors.affiliation: Mahatma Gandhi Institute of Technology, Gandipet, Hyderabad, 500 075, Telangana, India.
authors.forename: Ravichandar
authors.initials: R
authors.lastname: Maroju
authors.affiliation: Department of Biotechnolgy, Bharathidasan University, Tiruchirappalli, India.
authors.forename: K
authors.initials: K
authors.lastname: Baburao
authors.affiliation: Atlantis Phyto Tech, Subhas Nagar, Hyderabad, 500055, Telangana, India.
authors.forename: Lakshmana Swamy
authors.initials: LS
authors.lastname: Parasa
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D000890:Anti-Infective Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D060326:Chemistry Techniques, Synthetic; D015195:Drug Design; D006801:Humans; D008826:Microbial Sensitivity Tests; D062105:Molecular Docking Simulation; D009705:Nucleosides / Q000737:chemistry*; D011487:Protein Conformation; D021281:Quantitative Structure-Activity Relationship; D013806:Theophylline / Q000737:chemistry*; D014230:Triazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000737:chemistry / Q000378:metabolism
chemical_list: D000480:Alkynes; D000890:Anti-Infective Agents; D000970:Antineoplastic Agents; D009705:Nucleosides; D014230:Triazoles; D013806:Theophylline; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: 1,2,3-Triazoles; Antibacterial activity; Anticancer; Nucleoside; Theophylline