Identification of potent indolizine derivatives against Mycobacterial tuberculosis: In vitro anti-TB properties, in silico target validation, molecular docking and dynamics studies.

In the current study, two sets of compounds: (E)-1-(2-(4-substitutedphenyl)-2-oxoethyl)-4-((hydroxyimino)methyl)pyridinium derivatives (3a-3e); and (E)-3-(substitutedbenzoyl)-7-((hydroxyimino)methyl)-2-substitutedindolizine-1-carboxylate derivatives (5a-5j), were synthesized and biologically evaluated against two strains of Mycobacterial tuberculosis (ATCC 25177) and multi-drug resistant (MDR) strains. Further, they were also tested in vitro against the mycobacterial InhA enzyme. The in vitro results showed excellent inhibitory activities against both MTB strains and compounds 5a-5j were found to be more potent, and their MIC values ranged from 5 to 16 μg/mL and 16-64 μg/mL against the M.

Recent approaches in the drug research and development of novel antimalarial drugs with new targets.

Malaria is a serious worldwide medical issue that results in substantial annual death and morbidity. The availability of treatment alternatives is limited, and the rise of resistant parasite types has posed a significant challenge to malaria treatment. To prevent a public health disaster, novel antimalarial agents with single-dosage therapies, extensive curative capability, and new mechanisms are urgently needed.

Crystallography, Molecular Modeling, and COX-2 Inhibition Studies on Indolizine Derivatives.

The cyclooxygenase-2 (COX-2) enzyme is an important target for drug discovery and development of novel anti-inflammatory agents. Selective COX-2 inhibitors have the advantage of reduced side-effects, which result from COX-1 inhibition that is usually observed with nonselective COX inhibitors. In this study, the design and synthesis of a new series of 7-methoxy indolizines as bioisostere indomethacin analogues (-) were carried out and evaluated for COX-2 enzyme inhibition.

Current advances in the clinical development of anti-tubercular agents.

Tuberculosis (TB) is a communicable airborne infectious disease caused by the Mycobacterium tuberculosis (MTB) that primarily affects the lungs, and can disseminate to other parts of the body. MTB is one of the most dangerous pathogens, killing about 1.4 million people annually worldwide.

Current Scenario and Future Prospect in the Management of COVID-19.

The COVID-19 pandemic continues to wreak havoc worldwide due to the lack of risk assessment, rapid spreading ability, and propensity to precipitate severe disease in comorbid conditions. In an attempt to fulfill the demand for prophylactic and treatment measures to intercept the ongoing outbreak, the drug development process is facing several obstacles and renaissance in clinical trials, including vaccines, antivirals, immunomodulators, plasma therapy, and traditional medicines. This review outlines the overview of SARS-CoV-2 infection, significant recent findings, and ongoing clinical trials concerning current and future therapeutic interventions for the management of advancing pandemic of the century.

Cytotoxicity and Antimycobacterial Properties of Pyrrolo[1,2-]quinoline Derivatives: Molecular Target Identification and Molecular Docking Studies.

A series of ethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-3-carboxylates - and dimethyl 1-(substituted benzoyl)-5-methylpyrrolo[1,2-]quinoline-2,3-dicarboxylates - have been synthesized and evaluated for their anti-tubercular (TB) activities against H37Rv (American Type Culture Collection (ATCC) strain 25177) and multidrug-resistant (MDR) strains of by resazurin microplate assay (REMA). Molecular target identification for these compounds was also carried out by a computational approach. All test compounds exhibited anti-tuberculosis (TB) activity in the range of 8-128 µg/mL against H37Rv.

P1 Receptor Agonists/Antagonists in Clinical Trials - Potential Drug Candidates of the Future.

Background: Adenosine mediates various physiological and pathological conditions by acting on its four P1 receptors (A1, A2A, A2B and A3 receptors). Omnipresence of P1 receptors and their activation, exert a wide range of biological activities. Thus, its modulation is implicated in various disorders like Parkinson's disease, asthma, cardiovascular disorders, cancer etc.

7-Amino-2-aryl/hetero-aryl-5-oxo-5,8-dihydro[1,2,4]triazolo[1,5-a]pyridine-6-carbonitriles: Synthesis and adenosine receptor binding studies.

A series of novel 7-amino-5-oxo-2-substituted-aryl/hetero-aryl-5,8-dihydro[1,2,4]triazolo[1,5-a]pyridine-6-carbonitriles (4a-4t) was synthesized, characterized and evaluated for their binding affinity and selectivity towards hA , hA , hA and hA adenosine receptors (ARs). Compound 4a with a phenyl ring at 2-position of the triazolo moiety of the scaffold showed high affinity and selectivity for hA AR (K hA  = 0.076 μM, hA  = 25.

Synthesis and Bronchodilator Studies of Some Novel 6-Alkyl/Aryl-1,2,4-Triazino[4,3-c]Quinazolines.

A series of alkyl- and aryl-1,2,4-triazino[4,3-c]quinazolines (5a-h and 8a-h) were synthesized and characterized. The title compounds were evaluated for their in vivo bronchodilator activity on guinea pigs. All the test compounds exhibited good protection against histamine-induced bronchospasm.

Multistep, microwave assisted, solvent free synthesis and antibacterial activity of 6-substituted-2,3,4-trihydropyrimido[1,2-c]9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines.

A novel, efficient, microwave assisted route for the synthesis of 6-substituted-2,3,4-trihydropyrimido[1,2-c]-9,10,11,12-tetrahydrobenzo[b]thieno[3,2-e]pyrimidines in good yields has been developed. The intermediates, 2-substituted-4-[3-hydroxy(propyl-1-amino)]5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines were obtained by irradiating 2-substituted-4-chloro-5,6,7,8-tetrahydrobenzo[b]thieno[2,3-d]pyrimidines with 1-amino-propanol under basic conditions in a microwave oven. 4-Chlorothieno[2,3-d]pyrimidines were synthesized by microwave irradiation of equimolar mixture of 4-hydroxythieno[2,3-d]pyrimidines and phosphorus oxychloride.

Synthesis and antibacterial activity of some novel triazolothienopyrimidines.

A novel series of some novel 5-substituted-1,2,4-triazolo[4,3-c]8,9,10-trihydrocyclopenta/8,9,10,11,12-pentahydrocyclohepta[b]thieno[3,2-e]pyrimidin-3-thiones has been synthesized. The intermediates 4-chloro-2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidines were prepared by warming 2-substituted-5,6,7-trihydrocyclopenta/5,6,7,8,9-pentahydrocyclohepta[b]thieno[2,3-d]pyrimidin-4[3H]-ones with oxalyl chloride. Thieno[2,3-d]pyrimidin-4[3H]-ones were prepared by a novel, microwave assisted, solvent free, synthetic route under basic conditions hitherto unreported in the literature from ortho amino ester of thiophene.