BACKGROUND: Quantitative Structure-Activity Relationship (QSAR) studies describing the correlations between biological activity as dependent parameters and physicochemical and structural descriptors, including topological indices (TIs) as independent parameters, play an important role in drug discovery research. The emergence of graph theory in exploring the structural attributes of the chemical space has led to the evolution of various TIs, which have made their way into drug discovery. The TIs are easy to compute compared to the empirical parameters, but they lack physiochemical interpretation, which is essential in understanding the mechanism of action. OBJECTIVES: Hence, efforts have been made to review the work on the advances in topological indices, their physicochemical significance, and their role in developing QSAR models. METHODS: A literature search has been carried out, and the research article providing evidence of the physicochemical significance of the topological parameters as well as some recent studies utilizing these parameters in the development of QSAR models, have been evaluated. RESULT: In this review, the physicochemical significance of TIs have been described through their correlations between empirical parameters in terms of explainable physicochemical properties, along with their application in the development of predictive QSAR models. CONCLUSION: Most of these findings suggest a common trend of TIs correlation with MR rather than logP or other parameters; nevertheless, the developed models may be useful in both drug and vaccine development.

BACKGROUND: Genus Torilis (Apiaceae) known as hedge parsley, encompasses 11-13 species distributed worldwide and shows potential pharmacological uses. Its phytochemical pattern is highly diversified including many phenolic and terpenic compounds. OBJECTIVE: This research-review provides new highlighting of structural organizations, structure-activity trends, taxonomical, tissue and geographical distribution of phytocompounds of Torilis genus from extensive statistical analyses of available data. METHOD: In extenso, exploration of documented literature and statistical data analyses were applied to update the phytochemical pool of the genus under several aspects including structural diversity, geographical distribution, biological compartmentations and pharmacological activities. RESULTS: Phytoconstituents were classified into homogeneous clusters that revealed to be associated with chemical constitutions (aglycone types, chemical groups) and distributions (through species, tissues, geographical). About bioactivities, terpenes were studied from a pharmacological point of view with relatively high frequencies for antifungal, antibacterial, cytotoxic and anti-inflammatory activities. Preliminary structure-activity relationships were highlighted implying opposite effects between hydroxylation and methylation in favor of different activities. Crude extracts and isolated compounds have shown several biological activities (antibacterial, anticancer, antiangiogenic, antiproliferative, etc.), thus providing authentic scientific proof for their diverse uses in folk medicines. CONCLUSION: The phytochemistry of the genus Torilis promises important perspectives in matters of pharmacological activities. These perspectives call for further investments in pharmacology because of (i) unbalance between phenolic and terpenic compounds according to the countries and (ii) more advanced current states of structural elucidations compared to biological evaluations.

BACKGROUND: DNA methyltransferases (DNMTs) have been reported to be potential drug targets in various cancers. The major hurdle in inhibiting DNMTs is the lack of knowledge about different DNMTs and their role in the hypermethylation of gene promoters in cancer cells. Lack of information on specificity, stability, and higher toxicity of previously reported DNMT inhibitors is the major reason for inadequate epigenetic cancer therapy. DNMT1 and DNMT3A are the two DNMTs that are majorly overexpressed in cancers. OBJECTIVE: In this study, we have presented computational and experimental analyses of the potential of some natural compounds, withaferin A (Wi-A), withanone (Wi-N), and caffeic acid phenethyl ester (CAPE), as DNMT inhibitors, in comparison to sinefungin (SFG), a known dual inhibitor of DNMT1 and DNMT3A. METHODS: We used classical simulation methods, such as molecular docking and molecular dynamics simulations, to investigate the binding potential and properties of the test compounds with DNMT1 and DNMT3A. Cell culture-based assays were used to investigate the inactivation of DNMTs and the resulting hypomethylation of the p16INK4A promoter, a key tumour suppressor that is inactivated by hypermethylation in cancer cells, resulting in upregulation of its expression. RESULTS: Among the three test compounds (Wi-A, Wi-N, and CAPE), Wi-A showed the highest binding affinity to both DNMT1 and DNMT3A; CAPE showed the highest affinity to DNMT3A, and Wi-N showed a moderate affinity interaction with both. The binding energies of Wi-A and CAPE were further compared with SFG. Expression analysis of DNMTs showed no difference between control and treated cells. Cell viability and p16INK4A expression analysis showed a dose-dependent decrease in viability, an increase in p16INK4A, and a stronger effect of Wi-A compared to Wi-N and CAPE. CONCLUSION: The study demonstrated the differential binding ability of Wi-A, Wi-N, and CAPE to DNMT1 and DNMT3A, which was associated with their inactivation, leading to hypomethylation and desilencing of the p16INK4A tumour suppressor in cancer cells. The test compounds, particularly Wi-A, have the potential for cancer therapy.

BACKGROUND: Food grains' ability to promote health is widely recognized as a result of their rich nutritional profile and presence of antioxidants. AIM: The present study aimed to investigate the antioxidant, antidyslipidemic, and cardiac risk preventive effects of unpolished whole rice extracts of Keteki and Kola joha of Assam, India, and to profile the polyphenolic compounds present. METHODS: Whole unpolished rice samples were extracted with ethanol and the efficacy of the extract of both rice cultivars was evaluated against high-fat and high-sugar induced hyperlipidemia in rats. The effects of extracts on lipid profile, hepatic enzyme, endogenous antioxidants, lipid peroxidation, creatine kinase-NAc, lactate dehydrogenase, C-reactive protein and lipoprotein(s) were evaluated. Atherogenic indices were calculated to find the effect of the extract on cardiac risk. HPLC analysis of whole unpolished rice samples was also carried out to profile the polyphenolics present. RESULTS: HPLC analysis revealed the presence of gallic acid, vanillic acid, caffeic acid, sinapic acid, o-coumaric acid, t-coumaric acid, rosamarinic acid, chlorogenic acid, phytic acid in both rice samples. Protocatechuic acid, syringic acid, and p-coumaric acid were detected in keteki joha, and ferulic acid was detected in kola joha only. Ethanol extracts (200 and 400 mg/kg) of both rice varieties for 30 days significantly averted dyslipidemia, preserved the level of endogenous antioxidants, and prevented lipid peroxidation. Levels of creatine kinase-NAc, lactate dehydrogenase, C-reactive protein, and lipoprotein (a) were significantly (P < 0.01) less in the extract-treated group compared to the disease-control group. Extract treatment enhanced ApoA1 level while the reduced level of ApoB. ApoB/ApoA1 ratio was found more in the disease control group, which was significantly reduced in the extract-treated group. The atherogenic index, atherogenic coefficient, and cardiac risk ratio were reduced, while the cardioprotective index was enhanced in treatment groups. CONCLUSION: This paper profiled polyphenolic compounds for the first time. Keteki joha exhibited better results than Kola joha. Observations offer novel insights into the hypothesis for the first time that unpolished Keteki and Kola joha rice can be beneficial in averting hyperlipidemia and its associated coronary events.