A comprehensive review on anticancer evaluation techniques.

The development of effective anticancer strategies and the improvement of our understanding of cancer need analytical tools. Utilizing a variety of analytical approaches while investigating anti-cancer medicines gives us a thorough understanding of the traits and mechanisms concerned to cancer cells, which enables us to develop potent treatments to combat them. The importance of anticancer research may be attributed to various analytical techniques that contributes to the identification of therapeutic targets and the assessment of medication efficacy, which are crucial things in expanding our understanding of cancer biology. The study looks at methods that are often used in cancer research, including cell viability assays, clonogenic assay, flow cytometry, 2D electrophoresis, microarray, immunofluorescence, western blot caspase activation assay, bioinformatics, etc. The fundamentals, applications, and how each technique analytical advances our understanding of cancer are briefly reviewed.

New benzisoxazole derivative: A potential corrosion inhibitor for mild steel in 0.5 M hydrochloric acid medium -insights from electrochemical and density functional theory studies.

6-fluoro-3-(4-piperidinyl)-1,2-benzisoxazole. HCl (FPBH), a substituted benzisoxazole derivative, was prepared from isonipecotic acid and characterized using various spectroscopic techniques. Using electrochemical examinations such as potentiodynamic polarisation (PDP) and electrochemical impedance spectroscopic (EIS) technique, the corrosion mitigation capabilities of this compound for mild steel (MS) in 0.5 M HCl medium were investigated. Theoretical studies were performed using quantum chemical calculations and density functional theory (DFT). PDP results exhibited the mixed-type behavior of FPBH and showed a maximum efficiency of 94.5 % at 1 × 10-3 M. The development of a protective adsorbed layer of FPBH decreases the corrosion current density (icorr) and corrosion rate (CR). The EIS technique revealed that the rise in the charge transfer resistance (Rct) values and reduction in the thickness of the double-layer capacitance (Cdl) reflected the drop in corrosion rate. The adsorption of FPBH took place through physisorption by conforming Langmuir's isotherm. The DFT method was performed on the optimized structure of FPBH to get additional evidence on the action mode of FPBH with the metal surface.

Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF-κB in Human Breast Cancer Cells.

Nuclear factor kappa B (NF-κB) is a potential therapeutic target in breast cancer. In the current study, a new class of oxazine- and piperazine-linked pyrimidines was developed as inhibitors of NF-κB, overcoming the complexity of the oxazine structure found in nature and enabling synthesis under laboratory conditions. Among the series of synthesized and tested oxazine-pyrimidine and piperazine-pyrimidine derivatives, compounds 3a and 5b inhibited breast cancer cell (MCF-7) viability with an IC50 value of 9.17 and 6.29 µM, respectively. In silico docking studies showed that the pyrimidine ring of 3a and the 4-methoxybenzyl thiol group of 5b could strongly bind the p65 subunit of NF-κB, with the binding energies -9.32 and -7.32 kcal mol-1. Furthermore, compounds 3a and 5b inhibited NF-κB in MCF-7 breast cancer cells. In conclusion, we herein report newer structures that target NF-κB in BC cells.

Electrochemical Synthesis of New Isoxazoles and Triazoles Tethered with Thiouracil Base as Inhibitors of Histone Deacetylases in Human Breast Cancer Cells.

Histone deacetylases (HDACs) are an attractive drug target for the treatment of human breast cancer (BC), and therefore, HDAC inhibitors (HDACis) are being used in preclinical and clinical studies. The need to understand the scope of the mode of action of HDACis, as well as the report of the co-crystal structure of HDAC6/SS-208 at the catalytic site, provoked us to develop an isoxazole-based lead structure called 4-(2-(((1-(3,4-dichlorophenyl)-1H-1,2,3-triazol-4-yl)methyl)thio) pyrimidin-4-yl) morpholine (5h) and 1-(2-(((3-(p-tolyl) isoxazol-5-yl)methyl)thio) pyrimidin-4-yl) piperidin-4-one (6l) that targets HDACs in human BC cells. We found that the compound 5h or 6l could inhibit the proliferation of BC cells with an IC50 value of 8.754 and 11.71 µM, respectively. Our detailed in silico analysis showed that 5h or 6l compounds could target HDAC in MCF-7 cells. In conclusion, we identified a new structure bearing triazole, isoxazole, and thiouracil moiety, which could target HDAC in MCF-7 cells and serve as a base to make new drugs against cancer.

A comprehensive review on Covid-19 Omicron (B.1.1.529) variant.

The world has been combating different variants of SARS-COV-19 since its first outbreak in Wuhan city. SARS-COV-19 is caused by the coronavirus. The corona virus mutates and becomes more transmissible than earlier variants as the day passes. Till 24 November 2021, SARS-COV-19 has four variants Alpha, Beta, Gamma, and Delta, respectively. Among them, the delta variant caused severe havoc across the world. South Africa registered a new variant with the World Health Organization (WHO) on 24 November 2021, which is much more transmissible than previous variants. The WHO classified it as a variant of concern (VOC) on 26 November 2021 and called it the Greek letter Omicron (B.1.1.529), the fifteenth letter in the alphabet. Here a serious attempt was made to comprehend the omicron variant's origin, nomenclature, characteristics, mutations, the difference between delta and omicron variant, epidemiology, transmission, clinical features, impact on immunity, immune evasion, vaccines efficacy, etc.

Synthesis, Molecular Docking and Evaluation of 1,3,4-Oxadiazole-Isobenzofuran Hybrids as Antimicrobial and Anticancer Agents.

In drug discovery, the hybridization of bioactive pharmacophores is a powerful tool for targeting enzymes involved in cancer and microbial cell growth. A combination of 1,3,4-oxadiazole and isobenzofuran may improve the antitumor and antimicrobial properties of the hybrid molecules. A series of hybrid molecules having 1,3,4-oxadiazole and isobenzofuran were synthesized and structural characterization was done by FT-IR, 1 H-NMR, 13 C-NMR, and mass spectrometry. Molecular docking studies were performed to investigate binding interactions of compounds with proteins (PDB NO: 2R3J and 1GII), and the results were consistent with in vitro anticancer data. All the synthesized compounds were tested for antimicrobial activity against S. aureus, E. faecalis (Gram-positive) and E. coli and P. aeruginosa (Gram-negative) bacterial strains. Among the synthesized compounds, 7a and 7b displayed good activity against the tested bacterial strains. Also, compounds were tested for their anti-tumor activity against breast cancer (MCF-7) and colon cancer (HCT-116) cell lines via SRB assay. In comparison to doxorubicin (1.14 µM), hybrids 7e (4.32 µM), 7f (4.15 µM), 7g (4.66 µM), and 7h (4.83 µM) demonstrated comparable IC50 value against the HCT 116 cell line.

Coinage Metal N-Heterocyclic Carbene Complexes: Recent Synthetic Strategies and Medicinal Applications.

New weapons are constantly needed in the fight against cancer. The discovery of cisplatin as an anticancer drug prompted the search for new metal complexes. The successful history of cisplatin motivated chemists to develop a plethora of metal-based molecules. Among them, metal-N-heterocyclic carbene (NHC) complexes have gained significant attention because of their suitable qualities for efficient drug design. The enhanced applications of coinage metal-NHC complexes have encouraged a gradually increasing number of studies in the fields of medicinal chemistry that benefit from the fascinating chemical properties of these complexes. This review aims to present recent developments in synthetic strategies and medicinal applications of copper, silver and gold complexes supported by NHC ligands.

Antimycobacterial susceptibility evaluation of rifampicin and isoniazid benz-hydrazone in biodegradable polymeric nanoparticles against Mycobacterium tuberculosis H37Rv strain.

INTRODUCTION: Tuberculosis (TB) is the single largest infectious disease which requires a prolonged treatment regime with multiple drugs. The present treatment for TB includes frequent administration of a combination of four drugs for a duration of 6 months. This leads to patient's noncompliance, in addition to developing drug-resistant strains which makes treatment more difficult. The formulation of drugs with biodegradable polymeric nanoparticles (NPs) promises to overcome this problem. MATERIALS AND METHODS: In this study, we focus on two important drugs used for TB treatment - rifampicin (RIF) and isoniazid (INH) - and report a detailed study of RIF-loaded poly lactic-co-glycolic acid (PLGA) NPs and INH modified as INH benz-hydrazone (IH2) which gives the same therapeutic effect as INH but is more stable and enhances the drug loading in PLGA NPs by 15-fold compared to INH. The optimized formulation was characterized using particle size analyzer, scanning electron microscopy and transmission electron microscopy. The drug release from NPs and stability of drug were tested in different pH conditions. RESULTS: It was found that RIF and IH2 loaded in NPs release in a slow and sustained manner over a period of 1 month and they are more stable in NPs formulation compared to the free form. RIF- and IH2-loaded NPs were tested for antimicrobial susceptibility against Mycobacterium tuberculosis H37Rv strain. RIF loaded in PLGA NPs consistently inhibited the growth at 70% of the minimum inhibitory concentration (MIC) of pure RIF (MIC level 1 µg/mL), and pure IH2 and IH2-loaded NPs showed inhibition at MIC equivalent to the MIC of INH (0.1 µg/mL). CONCLUSION: These results show that NP formulations will improve the efficacy of drug delivery for TB treatment.

Synthesis and Antimicrobial Screening of Novel 4-Substituted Phenyl-5-[1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3-thiones.

The paper describes a convenient method for the preparation of 4-substituted phenyl-5-[1-(4-fluorophenyl)-1,3-dihydroisobenzofuran-5-yl]-2H-1,2,4-triazole-3-thiones. The structures of the synthesized compounds are established by the results of LCMS, (1)H NMR, (13)C NMR, and IR and elemental analyses. The mercaptotriazoles are indicated to be in thione form by (1)H NMR spectra. All the synthesized compounds have been screened for antibacterial and antifungal activities. Compounds 12d and 12h exhibit encouraging results, while the remaining compounds show moderate activities. On the basis of spectral studies, formation of 2-amino-1,3,4-thiadiazoles from the isobenzofuran acyl thiosemicarbazides 11(a-h) is ruled out.