Molecular docking, synthesis, and antimycobacterial activities of pyrrolyl hydrazones and their copper complexes

Figures & data

Figure 1 Reported anti-TB drugs obtained from PubMed database.

Abbreviation: TB, tuberculosis.

Figure 2 Designed anti-TB drugs (pyrrolyl Schiff bases and proposed structures of their complexes).

Abbreviation: TB, tuberculosis.

Figure 3 Synthetic route for the synthesis of pyrrolyl hydrazones.

Figure 4 Synthetic route for the synthesis of metal complexes.

Figure 5 (A) and (B) Docked view of ligand (compound 4e) in B chain of PDB 2X22.

Abbreviation: PDB, protein data bank.

Figure 6 Docked view of ligand (compound 7d) in B chain of PDB 2X22.

Abbreviation: PDB, protein data bank.

Table 1 Surflex-Dock scores (kcal/mol) of N′-(arylidene)-4-(2,5-dimethyl-1H-pyrrol-1-yl)benzohydrazides, N′-(arylidene)-4-(1H-pyrrol-1-yl)benzohydrazides, and their copper complexes

Compounds	C score^a	Crash score^b	Polar score^c
PT70	13.60	−0.96	2.13
4a	5.52	−2.24	0.00
4b	5.47	−2.29	0.71
4c	5.59	−3.68	0.48
4d	3.90	−2.91	2.26
4e	6.11	−1.67	0.00
4f	5.39	−1.62	0.00
4g	4.53	−1.85	0.00
4h	3.37	−4.22	0.00
4i	4.54	−1.24	0.00
4j	5.41	−0.68	0.00
4k	5.28	−1.66	1.09
5a	5.03	−1.26	1.04
5b	4.94	−1.07	0.00
5c	5.38	−2.09	0.00
5d	3.70	−1.21	0.00
5e	4.51	−3.24	0.00
5f	4.82	−1.19	0.44
6a	3.96	−1.53	2.08
6b	3.55	−4.30	1.12
6c	5.47	−4.39	0.10
6d	2.11	−3.27	0.95
6e	3.37	−4.22	0.00
6f	4.70	−0.95	0.00
6g	0.17	−2.90	0.00
6h	5.14	−1.24	0.00
6i	2.99	−6.49	1.17
6j	4.65	−1.24	0.00
6k	1.08	−8.86	0.00
7a	1.99	−6.46	0.00
7b	5.00	−2.50	1.16
7c	4.66	−2.87	0.84
7d	6.03	−3.45	0.00
7e	1.07	−10.42	0.00
7f	4.04	−4.09	0.00

Notes:

a C score integrates a number of popular scoring functions for ranking the affinity of ligands bound to the active site of a receptor and reports the output of total score;

b crash-score reveals the inappropriate penetration into the binding site. Crash scores close to 0 are favorable. Negative numbers indicate penetration;

c polar scores indicate the contribution of polar interactions to the total score; Bold values indicate the compounds with highest C score among all the docked compounds.

Abbreviation: C score, consensus score.

Table 2 Antitubercular activities of synthesized compounds (4a–k, 5a–f, 6a–k, and 7a–f)

Compounds	M. tuberculosis H37Rv MIC (μg/mL)	Compounds	M. tuberculosis H37Rv MIC (μg/mL)
4a	25	6a	12.5
4b	25	6b	12.5
4c	6.25	6c	3.12
4d	25	6d	12.5
4e	3.12	6e	3.12
4f	25	6f	25
4g	50	6g	25
4h	25	6h	12.5
4i	25	6i	25
4j	25	6j	12.5
4k	25	6k	12.5
5a	25	7a	12.5
5b	25	7b	6.25
5c	12.5	7c	6.25
5d	25	7d	3.12
5e	12.5	7e	6.25
5f	25	7f	12.5
Pyrazinamide	3.125	Streptomycin	6.25

Note: Bold values indicate compounds showing good MIC values.

Abbreviations: M. tuberculosis, Mycobacterium tuberculosis; MIC, minimum inhibitory concentration.

Table 3 In vitro antibacterial activity (MIC expressed in μg/mL)

Compounds	Gram positive		Gram negative
	S. aureus	B. subtilis	K. pneumoniae	E. coli
4e	50	25	6.25	3.12
6c	100	50	12.5	6.25
6e	>100	25	50	3.12
7b	100	50	6.25	12.5
7d	>100	>100	100	25
Ciprofloxacin	0.4	0.4	0.2	0.4
Norfloxacin	0.4	0.2	0.4	0.4

Note: Bold values indicate compounds with good MIC values.

Abbreviations: S. aureus, Staphylococcus aureus; B. subtilis, Bacillus subtilis; K. pneumoniae, Klebsiella pneumoniae; E. coli, Escherichia coli; MIC, minimum inhibitory concentration.