Current Topics in Medicinal Chemistry - Volume 22, Issue 32, 2022

Background: Diabetes mellitus (DM) is a well-known global metabolic disorder. For its treatment, glibenclamide (GLB) is very often prescribed. However, herbal drugs are considered effective and better alternatives due to their low risk of side effects. This study was conducted to determine the combined effects of GLB and Pterocarpus marsupium (PM, a commonly available Indian herb) extract for the effective and safe treatment of hyperglycemia in the mouse model. Methods: Healthy adult male mice were distributed into five groups (n=7 in each group). Group I acted as the control, whereas groups II, III, IV, and V were considered experimental groups which received a single dosage (150 mg/kg body weight) of alloxan (ALX) intraperitoneally (i.p.). In addition, groups III, IV, and V received a pre-standardized dose of GLB (500 μg/kg body weight), PM extract (150 mg/kg body weight), and GLB+PM, respectively, at the same doses as used in individual treatment, after the seventh day of ALX administration for 15 days and the alterations in different DM related parameters were evaluated. Results: ALX-induced hyperglycemia and other adverse effects were nearly normalized by GLB and PM co-treatment as evidenced by marked suppression in glucose, triglyceride, total-cholesterol, lipid-peroxidation, and lipid-hydroperoxides with an increase in antioxidants status and liver glycogen content. The positive effects were more pronounced when both GLB and PM were given, as compared to that of either of the drugs, administered alone. Liver ultra-structure, analyzed through histology and transmission electron microscopy revealed normalization of the ALX-induced damaged hepatocytes. The presence of epicatechin, the major phytoconstituent of the PM extract, as confirmed by high-performance liquid chromatography (HPLC), is responsible for its antioxidative and glucose-lowering activities. Conclusion: These findings reveal that PM, along with GLB, exhibits synergistic and better effects than the individual drug in regulating hyperglycemia and associated changes in alloxan-induced mice.

The infectious diseases caused by bacterial resistance to antibiotics constitute an increasing threat to human health on a global scale. An increasing number of infections, including tuberculosis, pneumonia, salmonellosis and gonorrhea, are becoming progressively challenging to cure owing to the ineffectiveness of current clinically used antibiotics and presents a serious health threat worldwide in medical community. The major concern of this global health threat is the ability of microorganisms to develop one or several mechanisms of resistance to antibiotics, making them inefficient to therapeutic treatment. The quest for discovering novel scaffold with antimicrobial property is particularly in great need to face future challenges in hospital and healthcare settings. Hence, the development of benzothiazoles is of considerable interest to medicinal chemists. Benzothiazole, being part of an important class of heterocyclic scaffold retains a wide spectrum of various attractive pharmacological activities. Antibiotic resistance represents an increasing burden comprising medical cost, hospital stay and mortality. Several derivatives containing a benzothiazole scaffold, reported in the literature, were found to display remarkable potencies towards diverse Grampositive and Gram-negative bacterial pathogens. The principal focus concerns the antibacterial potential of benzothiazole-based derivatives as antimicrobial agents interacting with targets in bacterial pathogens. In this review, we also disclose the significance of the benzothiazole moiety in the discovery of new antibacterial compounds, the potential of benzothiazole-based derivatives in the case of resistant bacterial strains, optimization of their antibacterial activity, and their future perspectives. The structure-activity relationship study and the mode of action of the title derivatives are highlighted too.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) is a novel strain of SARS coronavirus. The COVID-19 disease caused by this virus was declared a pandemic by the World Health Organization (WHO). SARS-CoV-2 mainly spreads through droplets sprayed by coughs or sneezes of the infected to a healthy person within the vicinity of 6 feet. It also spreads through asymptomatic carriers and has negative impact on the global economy, security and lives of people since 2019. Numerous lives have been lost to this viral infection; hence there is an emergency to build up a potent measure to combat SARS-CoV-2. In view of the non-availability of any drugs or vaccines at the time of its eruption, the existing antivirals, antibacterials, antimalarials, mucolytic agents and antipyretic paracetamol were used to treat the COVID-19 patients. Still there are no specific small molecule chemotherapeutics available to combat COVID-19 except for a few vaccines approved for emergency use only. Thus, the repurposing of chemotherapeutics with the potential to treat COVID-19 infected people is being used. The antiviral activity for COVID-19 and biochemical mechanisms of the repurposed drugs are being explored by the biological assay screening and structure-based in silico docking simulations. The present study describes the various US-FDA approved chemotherapeutics repositioned to combat COVID-19 along with their screening for biological activity, pharmacokinetic and pharmacodynamic evaluation.

Background: There is an urgent need for new antitubercular compounds. Modification of antimycobacterial isonicotinohydrazide at hydrazide N2 provided antimycobacterial active compounds. Objective: Combining this scaffold with various aliphatic amines that are also frequently present in antitubercular compounds, we have designed, synthesized, and evaluated twenty-three N- (cyclo)alkyl-2-(2-isonicotinoylhydrazineylidene)propanamides and their analogues as potential antimycobacterial compounds. By increasing lipophilicity, we intended to facilitate the penetration of mycobacteria's highly impermeable cell wall. Methods: The target amides were prepared via condensation of isoniazid and pyruvic acid, followed by carbodiimide-mediated coupling with yields from 35 to 98 %. The compounds were screened against Mycobacterium tuberculosis H37Rv and two nontuberculous mycobacteria (M. avium, M. kansasii). Results: All the derivatives exhibited low minimum inhibitory concentrations (MIC) from ≤0.125 and 2 μM against M. tuberculosis and nontuberculous mycobacteria, respectively. The most active molecules were substituted by a longer n-alkyl from C8 to C14. Importantly, the compounds showed comparable or even several-fold lower MIC than parent isonicotinohydrazide. Based on in silico predictions, a vast majority of the derivatives share suitable physicochemical properties and structural features for drug-likeness. Conclusion: Presented amides are promising antimycobacterial agents.