Synthesis, biological evaluation and computational study of novel isoniazid containing 4H-Pyrimido[2,1-b]benzothiazoles derivatives.

Synthesis of novel and potent hit molecules has an eternal demand. It is our continuous study to search novel bioactive hit molecules and as a part of this, a series of novel N'-isonicotinoyl-2-methyl-4-(pyridin-2-yl)-4H-benzo[4,5]thiazolo[3,2-a]pyrimidine-3-carbohydrazide analogs (5a-5n) were synthesized with good yields by the conventional method. The various novel compounds have been characterized and identified by many analytical technique such as IR, 1H NMR, 13C NMR, mass spectral analysis, and elemental analysis. All the synthetic analogs (5a-5n) are evaluated for their in vitro antibacterial and anti-mycobacterial activities against different bacterial strains. Molecular docking and Molecular dynamics studies were helped in revealing the mode of action of these compounds through their interactions with the active site of the Mycobacterium tuberculosis enoyl reductase (InhA) enzyme. The calculated ADMET descriptors for the synthesized compounds validated good pharmacokinetic properties, confirming that these compounds could be used as templates for the development of new Anti-mycobacterial agents.

Microwave-Assisted ZrSiO2 Catalysed Synthesis, Characterization and Computational Study of Novel Spiro[Indole-Thiazolidines] Derivatives as Anti-tubercular Agents.

In the current investigation, we prepared a series of novel spiro[indole-thiazolidines] derivatives (5a-5h) from 5-substituted isatin derivatives and thioglycolic acid (TGA) with ZrSiO2 as an efficient catalyst under microwave irradiation. The significant merits of this protocol have some significant merits such as simplicity in operation, simple, efficient workup, good practical yields of product and the employment of recyclable catalyst. All the new synthesized scaffold has been well characterized by various spectroscopic methods and elemental analysis. All the spiro scaffolds were subjected to in vitro anti-mycobacterial activity against the Mycobacterium tuberculosis (H37Rv) strain. We have carried out molecular docking study of our synthesized compounds. We also calculated theoretically ADME-Tox parameters for synthesized compounds.

Drug development against tuberculosis: Past, present and future.

Infection of Mycobacterium tuberculosis (MTB) was observed as early as 5000 years ago with evidence, which is a primeval enemy of the humanoid race. MTB is the pathogen which is responsible for causing the infectious disease tuberculosis; it remains a major cause of morbidity and mortality in poor low-income countries as well as in developing countries because of non-availability of reliable laboratory facilities. The current treatment for drug-resistant tuberculosis (TB) is lengthy, complex, and connected with severe harmful side effects and poor outcomes. The present cure against tuberculosis has substantial restrictions, in terms of their efficiency, side-effect outline, and complication of handling. Furthermore, the emergence of multi-drug resistant tuberculosis (MDR-TB) outbreaks during the 1990s and additionally in recent times the vast deadly strains of extensively drug-resistant tuberculosis (XDR-TB) and totally drug resistance tuberculosis (TDR-TB) is hampering efforts to control and manage tuberculosis (TB). As a result, novel methodologies for the treatment of multi-drug-resistant and extensive drug-resistant tuberculosis (TB) are severely desired. A number of new potential anti-tuberculosis drug candidates with novel modes of action have been entered in clinical trials in recent years. These agents are most likely to be effective against resistant strains. The treatment landscape is beginning to shift, with the recent approvals by Food and Drug Administration to the new TB drugs bedaquiline and delamanid. Also, the pipeline of potential new treatments has been fulfilled with several compounds in clinical trials or preclinical development with promising activities against sensitive and resistant MTB bacteria. An additional new chemical entity is also under development. The already existing drugs with their suggested mode of treatment as well as new probable anti-tuberculosis drug moieties which are at present in the pipeline has been summarized in this review.