In vitro and ex vivo efficacies of four series of benzo [b]thiophene-2-carboxylic acid derivatives were studied against Mycobacterium tuberculosis H37Ra (MTB). Benzo [b]thiophenes were also tested in vitro against multidrug resistant Mycobacterium tuberculosis H37Ra (MDR-MTB), and 7b was found to be highly active against A-and D-MDR-MTB/MTB (MIC ranges 2.73−22.86 μg/mL). The activity of all benzo[b]-thiophenes against M. bovis BCG (BCG) was also assessed grown under aerobic and under conditions of oxygen depletion. Compounds 8c and 8g showed significant activity with MICs of 0.60 and 0.61 μg/mL against dormant BCG. The low cytotoxicity and high selectivity index data against human cancer cell lines, HeLa, Panc-1, and THP-1 indicate the potential importance of the development of benzo [b]thiophene-based 1,3-diketones and flavones as lead candidates to treat mycobacterial infections. Molecular docking studies into the active site of DprE1 (Decaprenylphosphoryl-β-D-ribose-2′-epimerase) enzyme revealed a similar binding mode to native ligand in the crystal structure thereby helping to understand the ligand−protein interactions and establish a structural basis for inhibition of MTB. In summary, its good activity in in vitro and ex vivo model, as well as its activity against multidrug-resistant M. tuberculosis H37Ra in a potentially latent state, makes 7b an attractive drug candidate for the therapy of tuberculosis. KEYWORDS: Benzo[b]thiophene, MDR-MTB, M. Bovis BCG, cytotoxicity, molecular dockingA mong infectious widespread diseases, tuberculosis (TB) remains an active and major health problem worldwide. TB is the deadliest communicable disease, caused by the global emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) strains of TB along with acquired, primary, and cross resistance mycobacterium TB (MTB) strains. Despite the availability of first line and second line drugs regimen to treat the disease, still unacceptably TB continues to have high mortality and a global health threat. Resistance to first line anti-TB drugs has been linked to spontaneous mutations in many genes.1 The probability of resistance arising when rifampicin and isoniazid are used in combination is only one in 10 14 , sufficiently low to prevent resistance for either drug.2 As per WHO, the direct observed therapy strategy (DOTS) is the most effective means to prevent the emergence of drug resistance.3 As for those with HIV, several other inter-related factors like poverty, mobility of people from the countries where TB is prevalent, the long and complex TB regimen, and poor management of TB control programs 4 pose the resurgence of TB.Mycobacterium bovis Bacillus Calmette Guerin (BCG), an attenuated strain closely related to MTB, 5 infections in humans have been reported from many centuries ago. M. bovis infections have re-emerged and are causing TB in humans, due to mutations during the long in vitro propagation of this strain and, in particular, those who are HIV-positive. Owing to the appearance of drug resi...

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in Wiley Online Library (wileyonlinelibrary.com).Novel thieno [2,3-b]quinoline-2-carboxylic acid derivatives including β-diketone, pyrazole, and flavone were prepared under ultrasonication and evaluated for in vitro antioxidant and anti-inflammatory activities. Antioxidant activity was determined by DPPH radical scavenging method and anti-inflammatory activity by HRBC membrane stabilization method. Some of the Compounds showed good antioxidant activity, whereas, some of the compounds bearing pyrazole core showed good anti-inflammatory activity. Further in silico physicochemical properties were also calculated for good oral drug bioavailability and drug likeness of synthesized compounds.

A series of new pyrazolines (4a-4g) and isoxazolines (5a-5g) have been synthesized in good-to-excellent yield from the corresponding chalcones (3a-3g) under ultrasound irradiation. The newly synthesized compounds were characterized and screened for their in vitro antimicrobial activity against different bacterial and fungal strains by standard agar dilution method and in vitro antioxidant activity by using DPPH method. Some of the synthesized compounds displayed significant antimicrobial and antioxidant activity. Docking study of the synthesized compounds has been performed, and results showed good binding mode in the active site of fungal enzyme P450 cytochrome lanosterol 14 a-demethylase. ADMET properties of synthesized compounds showed good drug-like properties.

A green and expedient approach for the synthesis of dihydropyrano [2,3-c] pyrazoles via four-component reaction of ethyl acetoacetate, hydrazine hydrate, aromatic aldehydes and malononitrile at room temperature under ultrasound irradiation is described. The reaction has been catalyzed by thiamine hydrochloride in aqueous medium. This protocol afforded several advantages such as inexpensive, easily available catalyst, simple operational procedure, excellent yield, use of aqueous medium and ultrasound irradiation that is considered to be relatively eco-friendly.

The title compounds 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h and 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h have been synthesized from β‐diketones and chromones, respectively, having 5‐methyl‐3‐phenylisoxazole moiety. Substituted 2‐acetylphenyl 5‐methyl‐3‐phenylisoxazole‐4‐carboxylate 3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h were converted into 1‐(2‐hydroxyphenyl)‐3‐(5‐methyl‐3‐phenylisoxazole‐4‐yl)propane‐1,3‐dione 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h by Baker–Venketaraman transformation. Further, the cyclodehydration of diketone 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h with glacial acetic acid in conc. HCl at reflux gave corresponding substituted 2‐(5‐methyl‐3‐phenylisoxazole‐4‐yl)‐4H‐chromen‐4‐one 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h. The corresponding 5a, 5b, 5c, 5d, 5e, 5f, 5g, 5h react with hydrazine hydrate in presence of glacial acetic acid in ethanol at reflux to furnish 2‐(5‐5(5‐methyl‐3‐phenylisoxazole‐4‐yl)‐1H‐pyrazole‐3‐yl)phenol 6a, 6b, 6c, 6d, 6e, 6f, 6g, 6h. The structures of all newly synthesized compounds have been confirmed by IR, 1H NMR, mass spectral data, as well as elemental analysis. The synthesized compounds have been screened for their antimicrobial activity. Some of the compounds show better antimicrobial activity as compared with the reference drugs Streptomycin, Ampicillin, Gentamycin, Cefixime, and Ketoconazole.

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The synthesis of 4,4′‐(arylmethylene)bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ol) derivatives catalyzed by ʟ‐proline is a simple, versatile, and efficient method. In vitro antioxidant, anti‐inflammatory, and antimicrobial activities of compounds 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i, 4j were studied. Furthermore, to rationalize the observed anti‐inflammatory activity data, molecular docking study has been performed against COX‐2 enzyme which revealed a good binding affinity for these molecules and could provide an insight into the various bonded and non‐bonded interactions guiding their binding affinity.