Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

Salve, Preeti S.; Parchure, Prajakta; Araujo, Lisel; Kavalapure, Rohini S.; Jalalpure, Sunil S.; Sriram, Dharmarajan; Krishna, Vagolu Siva; Estharla, Madhu Rekha; Alegaon, Shankar G.

doi:10.1186/s43094-020-00162-7

Future Journal of Pharmaceutical Sciences

Table 2 Computed ADME properties of synthesized 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs (4a–o) by using QikProp module of the Schrodinger software

From: Design and synthesis of new 3-((7-chloroquinolin-4-yl)amino)thiazolidin-4-one analogs as Mycobacterium tuberculosis DNA gyrase inhibitors

Qikprop parameters and recommended values	MW (< 500)	DHB (< 5)	AHB (< 10)	QPlogPo/w (< 5)	QPlogS (− 6.5–0.5)	#rotor (0–15)	PSA (7–200)	QPlogHERG (concern below − 5)	QPP Caco (< 25 poor, > 500 great)	QPP MDCK (< 25 poor, > 500 great)	QPlogKhsa (− 1.5–1.5)	QPlogBB (− 3.0–1.2)	%HOA (> 80% is high, < 25% is poor)	RoF (≤ 4)	CNS (− 2.0 to + 2.0)
Compound
4a	373.832	1.0	5.0	4.1	− 5.511	2	54.211	− 5.385	1868.622	7031.998	0.389	0.115	100	0	1
4b	390.286	1.0	5	4.203	− 5.483	2	54.605	− 5.255	1870.338	6674.966	0.438	0.122	100	0	1
4c	390.286	1	5	4.389	− 5.938	2	54.205	− 5.488	1868.967	9608.051	0.473	0.162	100	0	1
4d	424.731	1	5	4.628	− 6.094	2	54.199	− 5.217	1869.515	10000.0	0.543	0.247	100	0	1
4e	424.731	1	5	4.711	− 6.254	2	54.208	− 5.243	1870.583	10000.0	0.558	0.276	100	0	1
4f	434.737	1	5	4.433	− 5.939	2	54.196	− 5.382	1862.466	10000.0	0.488	0.182	100	0	1
4g	452.728	1	5	4.637	− 6.24	2	54.206	− 5.363	1881.89	10000.0	0.534	0.25	100	0	1
4h	385.867	1	5.75	3.95	− 5.294	3	62.681	− 5.374	1911.71	3997.205	0.347	− 0.057	100	0	0
4i	415.893	1	6.5	3.929	− 5.126	4	70.827	− 5.061	2011.858	4224.013	0.298	− 0.087	100	0	0
4j	445.92	1	7.5	4.074	− 5.042	5	78.187	4.699	2155.439	4465.98	0.317	− 0.107	100	0	0
4k	400.839	1	6	3.149	− 5.211	3	98.555	− 5.352	227.236	399.945	0.293	− 0.981	87.563	0	− 1
4l	371.84	2	5.75	3.14	− 4.862	3	76.866	− 5.258	563.818	1068.03	0.21	− 0.558	94.571	0	0
4m	380.851	1	6.5	3.115	− 6.063	3	80.003	− 5.55	386.886	710.884	0.183	− 0.766	91.496	0	− 1
4n	398.909	1	6	4.4	− 6.005	3	56.846	− 5.572	2001.246	4199.933	0.529	− 0.065	100	0	0
4o	361.863	1	5	3.84	− 5.262	2	55.275	− 5.381	1762.935	5695.384	0.307	0.061	100	0	1
Ciprofloxacin	331.346	1	6	0.28	− 3.793	1	99.131	− 3.138	13.81	11.268	− 0.004	0.6	48.991	0	0
Pyrazinamide	123.114	2	5	− 0.631	0.536	1	77.823	− 3.215	301.732	135.482	− 0.819	− 0.71	67.629	0	− 1
Ethambutol	204.312	4	6.4	− 0.281	0.566	11	63.324	− 5.172	76.213	37.472	− 0.805	− 0.156	58.987	0	0

MW molecular weight of the molecule, DHB estimated number of hydrogen bonds that would be donated by the solute to water molecules in an aqueous solution, AHB estimated number of hydrogen bonds that would be accepted by the solute from water molecules in an aqueous solution, #rotor number of rotatable bonds, PSA polar surface area, QPlogPo/w predicted octanol/water partition coefficient, QPlogS predicted aqueous solubility, QPlogHERG predicted IC50 value for blockage of HERG K⁺ channels, QPP Caco predicted apparent Caco-2 cell permeability, QPP MDCK predicted apparent MDCK cell permeability, QPlogKhsa prediction of binding to human serum albumin, QPlogBB predicted brain/blood partition coefficient, %HOA percent human oral absorption, RoF rule of five, CNS predicted central nervous system activity

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