Host-mycobacteria conflict: Immune responses of the host vs. the mycobacteria TLR2 and TLR4 ligands and concomitant host-directed therapy

Combined Bioinformatics and Combinatorial Chemistry Tools to Locate Drug‐Able Anti‐TB Phytochemicals: A Cost‐Effective Platform for Natural Product‐Based Drug Discovery

“…A SAR analysis between two tetrahydrofuran-type phyto-constituents, beilschmin A (2.5 μg/mL) exhibited increased activity by presence of 4-methoxybenzo[d] [1,3]dioxole than 1,2,3-trimethoxybenzene B (7.5 μg/mL) (Figure 5A). From predicted drug-ability profiles (À 1.10 and À 0.64), both candidates had negative profiles belonging to the same toxicity class, IV.…”

“…From predicted drug-ability profiles (À 1.10 and À 0.64), both candidates had negative profiles belonging to the same toxicity class, IV. Thus, 4-methoxybenzo[d] [1,3]dioxole has a relatively strong activity, but the entire moiety is not sufficient to produce a positive drug-ability score. Even though there are different substitutions in dihydrobenzofuran neolignans such as, licarin A and B, both showed anti-TB activity at 3.1 μg/mL.…”

“…Even though there are different substitutions in dihydrobenzofuran neolignans such as, licarin A and B, both showed anti-TB activity at 3.1 μg/mL. Based on molecular docking and toxicity profiles, 2-methoxyphenol substituted licarin A obtained a comparatively higher docking score and belonged to toxicity class-V versus benzo[d] [1,3]dioxole substituted licarin B. However, both chemicals showed a negative drug-likeness score, which hindered their lead candidate status (Figure 5B).…”

“…[1] On the other hand, the failure of the front-line anti-TB drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA) and streptomycin (STM), the second-line anti-TB drugs, moxifloxacin (MXF), kanamycin (KAN), ethionamide (ETA) and para-aminosalicylic acid (PAS) including the combined directly observed treatment short-course (DOTS) against emerged multidrug-resistant (MDR)-TB and extensively drug-resistant (XDR TB strains to create a pandemic situation and one types of threatening to global communities. [2,3] From the last decade three anti-TB drugs, bedaquiline (BDQ), delamanid (DLM) and pretomanid (PMD), have been introduced as empiric anti-TB treatments. [2,4] As a result, the development of a newer anti-TB drug is slower than drug resistance development.…”

“…Approximately 10 million newly diagnosed TB cases (nearly 1.1 million children, 3.2 million women and 5.7 million men) have been reported each year, of which up to 8 million freshly diagnosed TB cases are reported from African and Asian nations [1] . On the other hand, the failure of the front‐line anti‐TB drugs, isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA) and streptomycin (STM), the second‐line anti‐TB drugs, moxifloxacin (MXF), kanamycin (KAN), ethionamide (ETA) and para ‐aminosalicylic acid (PAS) including the combined directly observed treatment short‐course (DOTS) against emerged multidrug‐resistant (MDR)‐TB and extensively drug‐resistant (XDR TB strains to create a pandemic situation and one types of threatening to global communities [2,3] …”