Design, Synthesis, Characterisation, and Evaluation of Substituted Quinolin-2-one Derivatives as Possible Anti-lung Cancer Agents.

BACKGROUND: According to 2022, the estimated number of cancer cases in India was found to be 1,461,427. Lung cancers are the leading cause of death among Indian males. Research on cancer has been conducted to develop better treatments that are safe and effective and could be used to diagnose cancer at an early stage. It was found that quinolin-2-one possesses anticancer activity, which led us to synthesize substituted quinolin-2-one derivatives that can provide a longer future to cancer patients and decrease the risk of dying from cancer. OBJECTIVE: This study aimed to carry out the design, synthesis, characterisation, and evaluation of novel substituted quinolin-2-one analogues as possible anti-lung cancer agents. METHOD: Compound III a/III b on reaction with acids, sodium acetate and ethylchloroacetate, substituted benzaldehyde, phthalic anhydride, and 2N sodium hydroxide yielded compounds IV a/ IV b, V a/ V b, VI a/ VI b, VI c/ VI d, VI e/ VI f, VII a/ VII b, and VIII a/ VIII b, respectively. RESULT: Among all the synthesised derivatives, compound VII a was found to be most potent with a MolDock score of -132.78 as compared to standard drug imatinib (-114.37) and active ligand 4- anilinoquinazoline (-126.71). All the synthesized derivatives showed a good ADME profile, but compound VII a showed the best ADME data among all the synthesised derivatives. All the synthesised compounds were tested for their in vitro anticancer activity against the Hop-62 (human lung cancer) cell line, out of which compound VII a was found to be most potent, with a percent control growth of -51.7% at a concentration of 80µg/ml, which was in comparable to the positive control, Adriamycin (-70.5%) and standard imatinib (-84.0%). CONCLUSION: Compound VII a showed the highest MolDock score and was most potent against human lung cancer cell line Hop-62.

Design, Docking, Characterisation, and Synthesis of Pyrimidine Derivatives for Antidepressant Activity.

BACKGROUND: According to the report, in 2022, the prevalence rate of depression in India was 4.50%, and the cases stood at 56,675,969. The development of antidepressant agents has reduced the number of depressant and suicidal cases. Many researchers have found that pyrimidine possesses antidepressant activity. With this background, we thought of synthesizing pyrimidine derivatives. OBJECTIVE: The objective of this study is to carry out molecular docking, synthesis, characterization, and evaluation of 2-((4,6-diphenylpyrimidin-2-yl)oxy)-N-phenylacetamide derivatives (17-26) as in vivo antidepressant agent. METHOD: The designed compounds were checked for their activity using Molegro virtual docker (MVD) and were further synthesized. Benzaldehyde reacted with acetophenone to give compound (3), which gave compound (4) upon reaction with urea. In another reaction, substituted anilines (5) were reacted with chloroacetyl chloride (6) to yield compounds (7-16), which upon further reaction with compound (4) yielded the final derivatives (17-26). The synthesized compounds were characterized by spectral analysis and checked for their antidepressant activity. RESULT: The MolDock scores of the derivatives ranged from -147.097 to -182.095, whereas of active ligand IXX_801 was -115.566. All the synthesized pyrimidine derivatives showed better affinity towards the Cryo-EM structure of the wild-type human serotonin transporter complexed with vilazodone, imipramine, and 15B8 Fab protein (PDB ID: 7LWD) as compared to standard drug clomipramine (-101.064). All the synthesized derivatives were screened for antidepressant activity at a 100mg/kg dose level compared to the standard clomipramine HCl at a dose level of 20mg/kg. Among all the synthesized derivatives, compound 24 showed the most potent antidepressant activity, and Compound 20 showed moderate antidepressant activity, which reduced the duration of immobility times to 35.42% and 31.97% at 100mg/kg dose level when compared to the control, respectively. CONCLUSION: Compound 24 showed the highest MolDock score as well as found to be the most potent antidepressant agent.

Identification of Linomide Derivatives as Potential Anticancer Therapeutics using Molecular Docking Studies.

12 analogs bearing a structural similarity to Linomide, a bonafide anticancer agent were synthesized wherein cyclization of substituted dianilides rendered 4-hydroxyquinolin-2(1H)-ones that were subjected to a Mannich reaction to yield 4-hydroxy-3-(substituted-1-ylmethyl) quinolin-2(1H)-one analogs. Characterization was performed using IR, 1H nuclear magnetic resonance and 13C NMR spectral analysis. Subsequently, in vitro anticancer studies revealed that Compound 4b showed maximum cytotoxicity with IC50 values of 1.539 µM/ml and 1.732 µM/ml against A549 and K562 cell lines respectively. This, however, is lower in comparison with standard Paclitaxel (IC50 values of 0.3 µM/ml for both cell lines). Surprisingly, docking studies at the active site of EGFRK revealed Compound 4b possessed a MolDock Score of -110.2253 that is highly comparable to the standard 4-anilinoquinazoline (MolDock Score of -112.04). Our computational and biological data thus provides an insight on the cytotoxicity of these derivatives and warrants future research that can possibly lead to the development of potent anticancer therapeutics.