In this study, two series of imidazopyridine-linked thiazolidinone rings (5a-h and 6a-h) constituting 16 new compounds were synthesized and tested for their antiproliferative activity against a panel of three human cancer cell lines, that is, MCF-7 (human breast cancer), A549 (human lung cancer), and DU145 (human prostate cancer). Three compounds, 5h, 6f, and 6h, exhibited remarkable results against all three cell lines, but compound 6h was found to be the most active one against the breast cancer cell line. Among all the synthesized compounds, 6h displayed the highest antioxidant results. Furthermore, the potent compounds 5h, 6f, and 6h showed no signs of toxicity at doses ranging from 50 to 500 mg/kg of animal body weight. The biochemical parameters (SGOT and SGPT) of compound 6h nearly matched the control in hepatotoxicity studies. The molecular docking and MM-GBSADG binding studies are in agreement with the in vitro anticancer and antioxidant activity results. The most promising compound 6h was found to have the highest docking score and binding energy, and its absorption, distribution, metabolism, and excretion (ADME) parameters are in the acceptable range. Thus, it can be concluded that 6h, an imidazopyridine derivative endowed with a thiazolidinone ring system, has the potential to be developed as an anticancer agent.
A series of benzimidazole‐derived–furanones (4a–l) were synthesized, characterized, and explored for their in vitro anticancer activities. The pharmacokinetic parameters assessed revealed that all the compounds followed the Lipinski's rule of five, making them potential drug candidates. Further, the results of anticancer activity revealed that (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐(3,4,5‐trimethoxybenzylidene)furan‐2(3H)‐one (4a), was active against A549, MCF7, and DU145 with an IC50 values of 10.4 ± 0.39, 11.1 ± 0.43, and 10.7 ± 0.19 μM, respectively. While another compound (E)‐5‐(1H‐benzo[d]imidazol‐2‐yl)‐3‐([5‐phenyl]furan‐2‐yl)furan‐2(3H)‐one (4k) also exhibited good activity against A549, MCF7, and DU145 with IC50 values of 11.4 ± 0.39, 9.1 ± 0.43, and 12.7 ± 0.19 μM, respectively. Doxorubicin was used as the standard drug. Further, molecular docking studies were carried out to provide binding mode into the binding sites of vascular endothelial growth factor receptor (VEGFR). Docking scores and binding energies corroborated well with the results of experimental anticancer activity. Pharmacokinetic (ADME) parameters of the potent derivatives were also found to be in an acceptable range. The benzimidazole‐furanonone conjugates seem to be a potential source for the further development of potent cytotoxic agents.
Indian mustard (Brassica juncea L.) germplasm consisting 167 accessions including one check cultivar was evaluated for qualitative and quantitative traits. The present study was conducted to investigate genetic diversity and correlation among studied genotypes of B. juncea L. based on agro-morphological at NARC, Islamabad, Pakistan. To investigate the genetic diversity based on morphological characters, data was recorded on 20 quantitative and 12 qualitative traits. The calculated data was analyzed through two complementary methods, i.e. PCA (Principal Component Analysis) and cluster analysis. Among all the studied cultivars, significant diversity was recorded for different agro-morphological characters. Among all the parameters, maximum variance was recorded for pod shattering (427.2) followed by plant height (345.6), days to 100% flowering (336.2) and main raceme length (210.0). Among all the characters, the greatest and highly significant association (0.99) was found between days to maturity 50% and days to maturity 100% followed by correlation (0.86) among days to flowering 50% and days to flowering 100%, correlation value (0.71) was calculated among leaf length and leaf width. Using cluster analysis all the genotypes were divided into five major groups. It was observed that 7 out of 20 principal components with an Eigen value of ≥1.0 calculated for 73.92% of the total diversity observed between 167 accessions of Indian mustard (B. juncea L.). The contribution of first three PCs in the total PCs was 23.25, 12.87 and 11.24, respectively. Among all the investigated accessions two genotypes 26,813 and 26,817 showed great How to cite this paper: Saleem, N., Jan, S.A., Atif, M.J., Khurshid, H., Khan, S.A., Abdullah, M., Jahanzaib, M., Ahmed, H., Ullah, S.F., Iqbal, A., Naqi, S., Ilyas, M. 70potential for seeds/silique, 1000-seed weight and seed yield/plant, respectively, so these genotypes are recommended for future breeding programs for achieving promising results.
Forced degradation studies include the degradation of new drug substance and drug product at conditions more severe than accelerated conditions. These studies illustrate the chemical stability of the molecule which further facilitates the development of stable formulation with suitable storage conditions. ICH guidelines demonstrate certain degradation conditions like light, oxidation, dry heat, acidic, basic, hydrolysis etc. ICH Q1A, QIB and Q2B exemplify the forced degradation studies. This review overviews the strategic approaches and trends in forced degradation studies.
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