Synthesis, Anti-Bacterial and Molecular Docking Studies of Arylated Butyl 2-Bromoisonicotinate Against Clinical Isolates of ESBL-Producing Escherichia coli ST405 and Methicillin-Resistant Staphylococcus aureus

Figures & data

Figure 1 Phenotypic Confirmation of MRSA.

Table 1 MIC (mg/L) of Antibiotics Against ESBL-Producing E. coli ST405 and MRSA

Isolates	P ≥0.25	SAM ≥32	PIP ≥128	FOX ≥8	CRO ≥64	FEP ≥64	ATM ≥64	MEM ≥16	LEV ≥8	MXF ≥8	MNO ≥16	TE ≥16	TGC ≥8	C ≥64	TMP ≥16	VAN ≥16	CS ≥16	LZD ≥8
E. coli	NA	≥32	≥128	NA	≥64	≥64	≥64	≥16	≥8	≥8	≥16	≥16	1	≥32	≥16	NA	≤0.5	NA
MRSA	≥32	NA	NA	≥32	≥64	NA	NA	≥16	≥8	≥8	≥16	≥16	NA	≥32	≥16	1	NA	2

Abbreviations: P, Penicillin; SAM, Ampicillin/sulbactam; CRO, Ceftriaxone; PIP, Piperacillin; MEM, Meropenem; ATM, Aztreonam; FEP, Cefepime; LEV, Levofloxacin; MXF, Moxifloxacin; MNO, Minocycline; TGC, Tigecycline; TE, Tetracycline; C, Chloramphenicol; TMP, Trimethoprim; LZD, Linezolid; Van, Vancomycin; CS, Colistin; NA, Not applicable.

Figure 2 An overview of synthesis of butyl 2-bromoisonicotinate (3) and its derivatives (5a–5h) via SMC reaction.

Table 2 Zone of Inhibition (mm) of ESBL-Producing E. coli ST405 Agar Well Diffusion Assay

Molecule No.	Zone (mm) (50mg)	Zone (mm) (40mg)	Zone (mm) (30mg)	Zone (mm) (20mg)	Zone (mm) (10mg)	Zone (mm) (5mg)	Zone (mm) DMSO
3	29	18	17	13	11	9	0
5a	15	13	11	9	8	7	0
5d	14	13	10	9	8	6	0
5e	12	10	9	8	7	5	0
5f	9	0	0	0	0	0	0
5h	10	0	0	0	0	0	0

Table 3 Zone of Inhibition (mm) of MRSA by Agar Well Diffusion Assay

Molecule No.	Zone (mm) (50mg)	Zone (mm) (40mg)	Zone (mm) (30mg)	Zone (mm) (20mg)	Zone (mm) (10mg)	Zone (mm) (5mg)	Zone (mm) DMSO
3	18	13	12	10	9	7	0
5a	24	17	15	12	10	8	0
5d	21	19	18	17	15	12	0
5e	8	0	0	0	0	0	0
5f	9	0	0	0	0	0	0
5h	8	0	0	0	0	0	0

Table 4 MIC (w/v) and MBC (w/v) of Different Molecules Against ESBL-Producing E. coli ST405

Molecule No.	MIC (mg/mL)	MBC (mg/mL)
3	0.78	1.56
5a	3.12	6.25
5d	6.25	12.5
5e	25	50
5f	25	50
5h	25	50

Table 5 MIC (w/v) and MBC (w/v) of Different Molecules Against MRSA

Molecule No.	MIC	MBC
3	0.78	1.56
5a	1.56	3.12
5d	6.25	12.5
5e	25	50
5f	25	50
5h	25	50

Figure 3 MIC of the ESBL-producing E. coli ST405 and MRSA isolate X-axis are the isolates, and Y-axis is the different concentrations of the molecules, -ve: negative control +ve: positive control.

Figure 4 MBC of the molecule (3) against ESBL producing E. coli ST405.

Table 6 Binding Energies and Interaction Pattern of the Parent Molecule (3) and Its Analogues (5a–h)

Molecule	Binding Energies (kJ mol^−1)	Hydrophobic Interactions	Hydrogen bonding Interactions
3	−4.5	Trp95, Ile71	Nil
5a	−4.3	Arg76, Val77	Nil
5b	−3.9	Arg76	H-acceptor: Val77
5c	−3.4	Nil	H-acceptor: Val77
5d	−3.7	Nil	H-acceptor: Val77
5e	−2.9	pi-H: Lys78	Nil
5f	−3.5	Nil	H-acceptor: Tyr17
5g	−3.05	pi-H: Arg76	Nil
5h	NA	Nil	Nil

Figure 5 The best and stable conformations of the highly active synthesized molecules (5a and 5b) including parent molecule (3). (A) Molecule (3) forming 2 hydrophobic bonds with Ile71 and Trp95. (B) Molecule (5a) forming 2-hydrophobic bonds with Arg76 and Val77. (C) Molecule (5b) forming 1H bond and 1-hydrophobic bonds with Val77 and Arg76.