We created thiazole and oxazole analogues of diaminopimelic acid (DAP) by replacing its carboxyl groups and substituting sulphur for the central carbon atom. Toxicity, ADME, molecular docking, and in vitro antimicrobial studies of the synthesized compounds were carried out. These compounds displayed significant antibacterial efficacy, with MICs of 70–80 µg/mL against all tested bacteria. Comparative values of the MIC, MBC, and ZOI of the synthesized compound were noticed when compared with ciprofloxacin. At 200 µg/mL, thio-DAP (1) had a ZOI of 22.67 ± 0.58, while ciprofloxacin had a ZOI of 23.67 ± 0.58. To synthesize thio-DAP (1) and oxa-DAP (2), l-cysteine was used as a precursor for the L-stereocenter (l-cysteine), which is recognized by the dapF enzyme’s active site and selectively binds to the ligand’s L-stereocenter. Docking studies of these compounds were carried out using the programme version 11.5 Schrodinger to reveal the hydrophobic and hydrophilic properties of these complexes. The docking scores of compounds one and two were −9.823 and −10.098 kcal/mol, respectively, as compared with LL-DAP (−9.426 kcal/mol.). This suggests that compounds one and two interact more precisely with dapF than LL-DAP. Chemicals one and two were synthesized via the SBDD (structure-based drug design) approach and these act as inhibitors of the dapF in the lysine pathway of bacterial cell wall synthesis.

Background: Tuberculosis is a highly contagious disease that is one of the major causes of mortality worldwide and the leading infectious organism-related cause of death. Various tetrazole and quinazoline compounds have been successfully developed in the past for tuberculosis treatment. In this case, we planned to design the hybrid moieties by combining both tetrazole and quinazoline nucleus to create novel compounds with increased activity. Methods: 6, 6-dimethyl-5, 6, 7, 9–tetrahydrotetrazolo [5, 1-b] Quinazolin-8(4H) -one derivatives were synthesized, characterized by using spectral data. The antitubercular activity of the synthesised compounds was tested against the H37RV strain of Mycobacterium tuberculosis. In order to identify the interactions with the target protein Mtb Pks13 Thioesterase domain in complex with inhibitor, docking analysis of the final compounds was performed (Protein data bank ID: 5V41). To verify their drug-like potential, the synthesised compounds were subjected to Pharmacokinetic prediction experiments. Zebrafish larvae had been used to test the teratogenicity of the synthesised compounds. Results: At 6.25 µg/mL, compounds F4 and F7 exhibited good efficacy against Mycobacterium tuberculosis strains. Docking studies aided in determining the most likely binding mode within the binding cavity of the concerned target protein. Conclusion: Compounds containing p-fluorophenyl and p-nitrophenyl groups as substituents were found to have excellent anti-tubercular activity.

A rapid and efficient method has been developed for the synthesis of pyrazolo[3,4-d]pyrimidines (5a-j) via microwave assisted method as well as conventional method using four components system in the presence of ionic liquid 2-methyl-imidazolium thiocyanate as a green catalyst. It was found that ionic liquid showed better reactivity than p-toluene-sulfonic acid (p-TSA) and L-proline. All the synthesized pyrazolo-pyrimidine derivatives were characterized by FT-IR, 1H NMR, 13C NMR spectral and elemental analysis. Further, the in vitro anti-breast cancer activity was evaluated by performing cytotoxicity studies against MCF-7 cell lines at different concentrations of synthesized compounds ranging from 100 to 500 µg/mL. Among the series of compounds, compounds 5a and 5d showed significant cytotoxic effect at the lowest concentration. However, all the synthesized compounds proved to be efficient against inhibiting breast cancer cells.