![conference banner](/images/conference-banner.jpeg)
Abstract
Aim: Frequent use of antibiotics is responsible for the development of antibiotic resistance; thus, there is an urgent need for the development of new antibacterial agents that act by novel mechanism pathways.
Objective: The aim of the study was to develop hybrid novel 4-aminoquinoline 1,3 5-triazine derivatives and determine their antibacterial activity.
Methods: Novel hybrid 4-aminoquinoline 1,3,5-triazine derivatives were synthesized by nucleophilic substitution and characterized by different spectroscopic methods. Furthermore, in silico study was carried out with 16S-rRNA A-site (PDB id: 1J7T using Discovery Studio 2018 software) to exemplify key structural interactions. In vitro antibacterial activity of target compounds was evaluated against three Gram-positive and three Gram-negative bacterial strains.
Results: In silico results have shown compound 8c to have both hydrophobic interactions (conventional hydrogen bond interactions with A A:16, A A:17 and carbon hydrogen bond with U A:14, G A:15) and hydrophilic interactions (G A:18G A:13, G A:15 and U A:19) along with excellent CDocker energy (- 28.2942). In vitro antibacterial results revealed that compound 8c showed better zone of inhibition against S. aureus (gram-positive) and E. coli (gram-negative) as compared to standard drug Cefixime.
Conclusion: Our study demonstrated that in silico study supported the experimental study, and the developed 1,3,5-triazine-4-aminoquinoline derivatives may be used as potential leads for future antibacterial drug development.
Keywords: Synthesis, docking, aminoquinoline, triazine, antibacterial activity, SAR analysis.
[http://dx.doi.org/10.24911/IJMDC.51-1549060699]
[http://dx.doi.org/10.1186/s13756-017-0208-x] [PMID: 28515903]
[http://dx.doi.org/10.1002/jor.23656] [PMID: 28722231]
[http://dx.doi.org/10.1016/j.msec.2019.01.094] [PMID: 30889703]
[http://dx.doi.org/10.1016/j.jallcom.2019.02.255]
[http://dx.doi.org/10.1016/j.compositesb.2019.05.047]
[http://dx.doi.org/10.1093/jac/dky019] [PMID: 29438542]
[http://dx.doi.org/10.1016/j.jallcom.2019.153186]
[http://dx.doi.org/10.1016/j.seppur.2020.117526]
[http://dx.doi.org/10.1016/j.chemosphere.2020.129293] [PMID: 33348263]
[http://dx.doi.org/10.1016/S2213-2600(21)00230-7] [PMID: 34000239]
[http://dx.doi.org/10.1039/C7NP00006E] [PMID: 28530279]
[http://dx.doi.org/10.1016/j.ecoenv.2020.111712] [PMID: 33396043]
[http://dx.doi.org/10.1128/CMR.00077-17] [PMID: 29540434]
[http://dx.doi.org/10.1007/s00044-010-9446-7]
[http://dx.doi.org/10.1111/j.1747-0285.2012.01430.x] [PMID: 22702334]
[http://dx.doi.org/10.1111/j.1747-0285.2012.01433.x] [PMID: 22716235]
[http://dx.doi.org/10.1016/j.bmcl.2014.05.103] [PMID: 24961639]
[http://dx.doi.org/10.1111/cbdd.13695] [PMID: 32333828]
[http://dx.doi.org/10.1016/j.tet.2006.07.039]
[http://dx.doi.org/10.1016/j.exppara.2015.06.016] [PMID: 26164360]
[http://dx.doi.org/10.3390/molecules23040746] [PMID: 29570685]
[http://dx.doi.org/10.1248/cpb.c14-00421] [PMID: 25273062]
[http://dx.doi.org/10.1039/C4RA16903D]
[http://dx.doi.org/10.3892/mmr.2018.9426] [PMID: 30152850]
[http://dx.doi.org/10.1016/j.ejmech.2018.11.027] [PMID: 30469039]
[http://dx.doi.org/10.3109/14756366.2012.755622] [PMID: 23327639]
[http://dx.doi.org/10.1002/jhet.3791]
[http://dx.doi.org/10.1007/s11030-019-10012-1] [PMID: 31705363]
[http://dx.doi.org/10.1039/c3nj00317e]
[http://dx.doi.org/10.1016/0022-2836(91)80222-G] [PMID: 1920412]
[http://dx.doi.org/10.1039/c2ra22353h]
[http://dx.doi.org/10.1007/s00044-013-0521-8]
[http://dx.doi.org/10.1007/s00726-007-0015-4] [PMID: 18180869]
[http://dx.doi.org/10.1074/jbc.M109.032334] [PMID: 19648119]
[http://dx.doi.org/10.1021/ar950135n] [PMID: 23618410]
[http://dx.doi.org/10.1002/prot.21253] [PMID: 17206656]
[http://dx.doi.org/10.1002/jhet.2210]