Contents lists available at ScienceDirect Journal of Microbiological Methods journal homepage: www.elsevier.com/locate/jmicmeth A facile one pot synthesis of novel pyrimidine derivatives of 1,5- benzodiazepines via domino reaction and their antibacterial evaluation Apoorva Misra a , Sonika Jain a , Dharma Kishore a , Vivek Dave b , Kakarla Raghava Reddy c , Veera Sadhu d, ⁎ , Jaya Dwivedi a, ⁎ , Swapnil Sharma b a Department of Chemistry, Banasthali Vidyapith, Rajasthan 304022, India b Department of Pharmacy, Banasthali Banasthali Vidyapith, Rajasthan 304022, India c School of Chemical and Biomolecular Engineering, The University of Sydney, Sydney, NSW 2006, Australia d School of Physical Sciences, Banasthali Vidyapith, Rajasthan, 304022, India ARTICLE INFO Keywords: Antibacterial activity Bacteria Pyrimidine compounds 1,5-benzodiazepine Domino approach ABSTRACT A new series of pyrimidine (8, 14, 18 and 23) embellished analogues of 1,5-benzodiazepines were synthesized by the one-pot domino approach using the catalyst DABCO (1,4-diazabicyclo[2.2.2]octane). For each compound synthesized, anti-microbial efficacy was determined using broth microdilution assay and half maximal inhibitory concentration (IC 50 ). Furthermore, FESEM (Field emission scanning electron microscope) studies were also carried out to observe the effect of the structure of test compounds on the morphology of both Gram-positive (S. aureus) and Gram-negative (E. coli) cell walls. The leakage of nucleotides and their integral components from compromised bacterial cells was assessed by plotting the optical density (OD) with respect to time of exposure at 320 nm. Anti-bacterial studies revealed that compound 23 was most active against targeted bacterial species. Results of the antibacterial study indicated that all the test compounds possess significant antibacterial potential against targeted bacterial strains. Amongst all, in the FE-SEM study, compound 23 caused marked alteration in bacterial cell morphology and resulted in maximum leakage of cell nucleotides in bacterial strains as compared to controls. Further efforts are required to establish their efficacy as antibacterial agents in clinical management. 1. Introduction During the past few decades, synthetic organic chemistry has un- dergone profound changes, leading to the synthesis of highly complex molecules with improved regio-, chemo-, disastereo- and en- antioselective methods (Mayer et al., 2001). The formation of complex molecules from simple substrates in a cheap and eco-friendly manner is a difficult task in modern organic chemistry. To overcome these issues, domino reactions have been used for the proficient diastereo- and en- antioselective construction of complex molecules from simple sub- strates in a single step (Alba et al., 2009). Domino reactions (Tietze and Rackelmann, 2004) are highly efficient means for the synthesis of complex molecules containing multiple bonds from simple substrates in an ecologically, economically and atom economical manner (Chao et al., 2012). In recent years, organic nitriles have captured the attention of chemists for their widespread utilization in heterocyclic synthesis. Creation of heterocycles from active nitrile substrates (Frutos et al., 2013), such as enaminonitriles (Abdelrazek and Bahbouh, 2012), imi- date esters, amidoximes, nitrilium ion intermediates derived from ni- triles has been a rapid emerging subject and a large number of articles, journals and reports have continuously appeared that cover the pro- gress of this subject. 1,5-benzodiazepine derivatives are efficient precursors in the pre- paration of other fused ring compounds such as furano-, oxazino-, ox- adiazolo- or triazolo- benzodiazepines (Kaur, 2013). 1,5-Benzodiazepine constitutes a major class of therapeutic com- pounds. Various compounds of this category function as potent vir- ucides, tranquilizer, non-nucleoside inhibitors of HIV-1 reverse tran- scriptase (NNRTIs). They show anticonvulsant (Sarro et al., 2003), https://doi.org/10.1016/j.mimet.2019.105648 Received 3 March 2019; Received in revised form 2 June 2019; Accepted 2 June 2019 Abbreviations: DABCO, 1,4-diazabicyclo[2.2.2]octane; DMAD, dimethyl acetylenedicarboxylate; DMF, dimethylformamide; FE-SEM, Field emission scanning electron microscope; TLC, Thin layer chromatography; NNRTIs, non-nucleoside inhibitors of HIV-1 reverse transcriptase; HSV-1, herpes simplex virus type-1; HAV, hepatitis-A virus; MTCC, Microbial Type Culture Collection; DMSO, dimethylsulfoxide; PBS, phosphate buffered saline; OD, optical density; IC 50 , half maximal inhibitory concentration ⁎ Corresponding authors. E-mail addresses: veera.sadhu@gmail.com (V. Sadhu), jayadwivedi@yahoo.co.in (J. Dwivedi). Journal of Microbiological Methods 163 (2019) 105648 Available online 10 June 2019 0167-7012/ © 2019 Elsevier B.V. All rights reserved. T