Nitrogen-containing heterocycles are extensively studied compounds owing their exciting biological properties and their role as pharmacophores of considerable historical importance 1, 2. Synthesis of benzothiazole and Pyrazole based small molecules for better treatment of diseases has become an important therapeutic objective, given the wide-ranging side effects of existing molecules and rapid resistance developed to them. These small molecule nuclei are found in many. Such promising anticancer and antibacterial agents were evaluated up to advanced clinical stage 3.
Azo dyes based on heterocyclic amines have been developed, and the resultant dyes give higher tinctorial potency. For instance, amino-substituted thiazole and benzothiazole compounds pay for very electronegative diazo components and consequently, provide a pronounced bathochromic effect compared to the corresponding benzenoid compounds 4.
Mycobacteria have recently increased their virulence and tuberculosis (TB) is nowadays the most lethal infection in the World 5. Tuberculosis (TB) is caused by an aetiological agent Mycobacterium tuberculosis which is the single largest cause of death globally due to its infections. The organisms responsible for the disease are the bacteria (tubercle bacilli) – M. tuberculosis, Mycobacterium tuberculosis complex including m. bovis and m. africanum 6. TB is second only to AIDS in infectious disease mortality, and indeed co-infection with the bacterium underlies a large fraction of the deaths attributed to HIV 7- 9.
Tuberculosis is a wind-borne disease. It is transmitted from an infected person to healthy person due to: coughing, sneezing, spitting, Discharging mucus, kissing etc,. A large number of plants are used in Asia and Africa to treat tuberculosis and related symptoms such as chronic coughs and respiratory complaints 10, 11. New targets are a priority, since attacking the bacterium using multiple strategies provides the best means to prevent resistance 12.
The protein RpsA, which is ribosomal protein S1 of Mycobacterium tuberculosis (Mtb), was recently identified as a target of Pyrazinamide (PZA), based on its binding activity to the active form of PZA- Pyrazinoicacid (POA), 13. Inhibition of RpsA by POA, obstructs the translation of mRNAs 14, 15. Hence, the molecular docking studies of RpsAwith newly synthesized compounds were carried out and reported.
The binding and interaction between small molecules and biomolecules, are quite interesting works 16. Specially, DNA Binding studies of these small molecules to DNA are very important in the development of new therapeutic reagents and DNA molecular probes 17, 18. The interaction of small molecules with DNA can be classified as either covalentl or non-covalentl bonding. In a covalent bonding, the active part of a molecule bonds covalently to a nitrogen base of DNA such as guanine N7. The non-covalent DNA interactions further divided in to intercalative, electrostatic, groove binding along outside of DNA and minor groove by means of van der Waals contacts, hydrogen bonds and ionic interactions 19. Investigations of the interaction between deoxyribonucleic acid (DNA) and other molecules have captivated scientists over the past years because it is related to the replication and transcription of cells, mutation of genes, DNA targeted drugs, origins of some diseases, and action mechanisms of some synthetic chemical nucleases 20. DNA is the primary intracellular target of anticancer drugs; DNA can cause damage in cancer cells, blocking the division and resulting in cell death 21. A variety of small molecules interact reversibly with DNA, primarily through three modes: (i) electrostatic interactions (ii) binding interactions with grooves of DNA double helix; and (iii) intercalation between the stacked base pairs of native DNA 22. From the above-mentioned facts and based on the principle, we synthesized a series of novel dispersed azo dyes derived from 4, 5, 6, 7-tetrahydro-1, 3-benzothiazole-2-amine by diazo-coupling reaction, which was evaluated for in vitro antioxidant and antituberculosis activies. Subsequently, DNA binding studies were also carried out to investigate the mechanism of action of these compounds.