Bisbenzimidazoles: Anticancer Vacuolar (H⁺)-ATPase Inhibitors

Small molecule chemotherapeutic agents such as Imatinib, Gefitinib, and Erlotinib have played a significant role in the treatment of cancer. Although the unprecedented progress has been achieved in cancer treatment with these targeted agents, there is a strong demand for the development of selective and highly efficacious cancer drugs. V-ATPases are emerging as important target for the identification of novel therapeutic agents for cancer. Our screening and drug discovery processes have identified the bisbenzimidazole derivative (RP-15) as a potent anticancer V-ATPase inhibitor. In the present study, bisbenzimidazoles (compound-25, RP-11 and RP-15) have been tested for proton-pump inhibition activity in human hepatoma cell line (Huh7.5). RP-15 displayed comparable proton-pump inhibition activity to the standard Bafilomycin A1. We examined the antiproliferative activity of these analogs in two highly invasive and metastatic inflammatory breast cancer (IBC) cell lines (SUM 149PT and SUM190PT) along with Huh7.5. The compound-25 (SUM190PT: IC50 = 0.43±0.11 μM) and its structural analog RP-11 (SUM190PT: IC50 = 0.49±0.09 μM) have shown significant inhibition toward IBC cell lines. Additionally, RP-11 and RP-15 have demonstrated very good cytotoxicity toward the majority of cancer cell lines in the NCI 60 cell line panel

Palladium Nanoparticles Grafted onto Phytochemical Functionalized Biochar: A Sustainable Nanozyme for Colorimetric Sensing of Glucose and Glutathione

The devising and development of numerous enzyme mimics, particularly nanoparticles and nanomaterials (nanozymes), have been sparked by the inherent limitations imposed by natural enzymes. Peroxidase is one of the enzymes that is extensively utilized in commercial, medical, and biological applications because of its outstanding substrate selectivity. Herein, we present palladium nanoparticles grafted on Artocarpus heterophyllus (jackfruit) seed-derived biochar (BC-AHE@Pd) as a novel nanozyme to imitate peroxidase activity en route to the rapid and colorimetric detection of H2O2, exploiting o-phenylenediamine as a peroxidase substrate. The biogenically generated BC-AHE@Pd nanocatalyst was synthesized utilizing Artocarpus heterophyllus seed extract as the reducing agent for nanoparticle formation, while the residue became the source for biochar. Various analytical techniques like FT-IR, GC-MS, FE-SEM, EDS, TEM, SAED pattern, p-XRD, and ICP-OES, were used to characterize the BC-AHE@Pd nanocatalyst. The intrinsic peroxidase-like activity of the BC-AHE@Pd nanocatalyst was extended as a prospective nanosensor for the estimation of the biomolecules glucose and glutathione. Moreover, the BC-AHE@Pd nanocatalyst showed recyclability up to three recycles without any significant loss in activity

Carbazole Derivatives as Potential Antimicrobial Agents

Microbial infection is a leading cause of death worldwide, resulting in around 1.2 million deaths annually. Due to this, medicinal chemists are continuously searching for new or improved alternatives to combat microbial infections. Among many nitrogen-containing heterocycles, carbazole derivatives have shown significant biological activities, of which its antimicrobial and antifungal activities are the most studied. In this review, miscellaneous carbazole derivatives and their antimicrobial activity are discussed (articles published from 1999 to 2022)

Novel 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents

Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents. Liver fibrosis assays demonstrated that the compounds 3a and 3c show inhibitory activity towards human hepatic stellate cells (LX2) activation at 10 μM. The HCV NS3 and NS5A proteins in HCV subgenome-expressing cells were also significantly reduced in cells treated with 3a and 3c, suggesting the possible inhibitory role of the compounds in HCV translation/replication activities. We have also examined the reactivity of these compounds with medicinally-relevant metal compounds such as platinum and gold. The reactivity of these complexes with metals and during Mass Spectrometry suggests that CS bond cleavage is relatively facile

Novel 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents

Liver fibrosis is a critical wound healing response to chronic liver injury such as hepatitis C virus (HCV) infection. If persistent, liver fibrosis can lead to cirrhosis and hepatocellular carcinoma (HCC). The development of new therapies for preventing liver fibrosis and its progression to cancer associated with HCV infection remains a critical challenge. Identification of novel anti-fibrotic compounds will provide opportunities for innovative therapeutic intervention of HCV-mediated liver fibrosis. We designed and synthesized a focused set of 5-arylthio-5H-chromenopyridines as a new class of anti-fibrotic agents. Liver fibrosis assays demonstrated that the compounds 3a and 3c show inhibitory activity towards human hepatic stellate cells (LX2) activation at 10 μM. The HCV NS3 and NS5A proteins in HCV subgenome-expressing cells were also significantly reduced in cells treated with 3a and 3c, suggesting the possible inhibitory role of the compounds in HCV translation/replication activities. We have also examined the reactivity of these compounds with medicinally-relevant metal compounds such as platinum and gold. The reactivity of these complexes with metals and during Mass Spectrometry suggests that CS bond cleavage is relatively facile

Coumarin Triazoles as Potential Antimicrobial Agents

Currently, in hospitals and community health centers, microbial infections are highly common diseases and are a leading cause of death worldwide. Antibiotics are generally used to fight microbial infections; however, because of the abuse of antibiotics, microbes have become increasingly more resistant to most of them. Therefore, medicinal chemists are constantly searching for new or improved alternatives to combat microbial infections. Coumarin triazole derivatives displayed a variety of therapeutic applications, such as antimicrobial, antioxidant, and anticancer activities. This review summarizes the advances of coumarin triazole derivatives as potential antimicrobial agents covering articles published from 2006 to 2022