Synthesis and biological evaluation of anti-tubercular activity of Schiff bases of 2-Amino thiazoles.

Tuberculosis, an infectious disease, has been reported to cause the death of 1.5 million in 2018. Due to the emergence of Multi-Drug Resistant-TB, Extensively Drug Resistant-TB, and Totally Drug Resistant-TB, many first-line and second-line drugs have been found in-effective. New drugs introduced in TB regimens such as pretomanid, bedaquiline and linezolid have been associated with toxicities. Hence, there is an urgent need for introducing safe and cost-effective antitubercular drugs. In this study, a series of Schiff bases of 2-amino thiazoles were synthesized and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain by Microplate Alamar Blue assay (MABA) method. N-[4-(2-Amino-thiazol-4-yl)-phenyl]-benzamide derivative with 2-nitro (5c2), 4-hydroxy (5c4) substitution, 2-[4-(2-Amino-thiazol-4-yl)-phenyl]-isoindole-1,3-dione derivatives with 3,4,5-trimethoxy substitution (5b1) and the compound 1-[4-(2-Amino-thiazol-4-yl)-phenyl]-pyrrole-2,5-dione (4a) which is a maleic derivative bearing thiazole ring, exhibited good anti-tubercular activity (MIC 6.25 µg/ml). Drug likeness was also evaluated for all the synthesised compounds using Molinspiration software. All synthesized compounds fulfilled the parameters of the Lipinski rule of five and showed drug-like properties. Through this study, it was proved that thiazole analogues have good anti-tubercular potentials.

Design, Synthesis and In vitro Biological Activity of Some New 1,3- thiazolidine-4-one Derivatives as Chemotherapeutic Agents using Virtual Screening Strategies.

AIMS: Designing of a new series of derivatives possessing thiazolidine-4-one moiety, their virtual screening using various computational tools, synthesis of prioritized compounds, spectral characterization and biological evaluation along with the comparison of in silico & in vitro results. BACKGROUND: WHO has come up with a list of antibiotic-resistant "priority pathogens" i.e. families of bacteria, that pose the greatest threat to human health. Some virulent bacteria are focused in the present study namely Mycobacterium tuberculosis (multi drug resistant), Staphylococcus aureus (methicillin-resistant) Streptococcus pneumoniae, (penicillin-non-susceptible) and Pseudomonas aeruginosa (Carbapenem-resistant) One of the neglected pathogenic disease which needs an urgent attention is Leishmaniasis which has a major burden among the poorest segments of populations in Asia, Africa, and South America. OBJECTIVE: 1. To design of a series of new heteroaryl-1,3-thiazolidin-4-one derivatives. 2. To prioritize the molecules for synthesis using virtual screening techniques. 3. To synthesize the virtually predicted molecules via different synthetic schemes. 4. To characterize the synthesized molecules by spectroscopic analysis. 5. To evaluate the synthesized compounds for in vitro biological activity. METHODS: A series of new heteroaryl thiazolidine-4-one derivatives was designed and subjected to in silico prioritization using various virtual screening strategies. The prioritized thiazolidinone derivatives were synthesized and screened for their in vitro antitubercular, anticancer, antileishmanial and antibacterial (Staphylococcus aureus; Streptococcus pneumonia; Escherichia coli; Pseudomonas aeruginosa) activities. RESULTS: The compounds with electronegative substitutions exhibited positive antitubercular activity, the derivatives possessing a methyl substitution exhibited good inhibitory response against breast cancer cell line MCF-7 while the compounds possessing a hydrogen bond acceptor site like hydroxyl and methoxy substitution in their structures exhibited good in vitro antileishmanial activity. Some compounds exhibited potent activity against gram positive bacteria Pseudomonas aeruginosa as compared to the standards. CONCLUSION: The designed compounds exhibited good in vitro anti-infective potential which was in good agreement with the in silico predictions and they can be developed as important lead molecules for anti-infective and chemotherapeutic drug research.