Effect of OH substitution in 3-benzylchroman-4-ones: crystallographic, CSD, DFT, FTIR, Hirshfeld surface, and energy framework analysis.

3-Benzylchroman-4-ones (homoisoflavanones) are oxygen-containing heterocycles with a sixteen-carbon skeleton. They belong to the class of naturally occurring polyphenolic flavonoids with limited occurrence in nature and possess anti-inflammatory, antibacterial, antihistaminic, antimutagenic, antiviral, and angioprotective properties. Recently, we reported the synthesis and anticancer activity studies of fifteen 3-benzylchroman-4-one molecules, and most of them were proven to be effective against BT549 and HeLa cells. In this work, we report the single-crystal X-ray crystallographic studies of two molecules 3-[(2-hydroxyphenyl)methyl]-3,4-dihydro-2H-1-benzopyran-4-one and 3-[(2,4-dimethoxyphenyl)methyl]-3,4-dihydro-2H-1-benzopyran-4-one. The single crystals were grown using a novel laser-induced crystallization technique. We observed that the 3-benzylchroman-4-one derivative bearing OH substitution at the 2' position adopted different conformation due to formation of dimers through O-H⋯O, and C-H⋯O intermolecular hydrogen bondings. The role of OH substitution in the aforementioned conformational changes was evaluated using density functional theory (DFT), Hirshfeld surface, energy framework and FTIR spectroscopy analysis. In addition, we have carried out a Cambridge Structural Database (CSD) study to understand the conformational changes using five analogue structures. X-ray crystallographic, computational, and spectroscopic studies of 3-benzylchroman-4-ones provided an insight into the role of substitution at benzyl moieties in stabilizing the three-dimensional (3D) structures.

Evaluation of in vitro and in vivo anticancer potential of two 5-acetamido chalcones against breast cancer.

Two 5'acetamido chalcones, C1 and C2 were synthesized by Claisen-Schmidt condensation method and characterized by IR, LC-MS, 1H NMR and 13C NMR. These compounds were evaluated for anticancer activity in vitro in breast cancer cell lines (MCF-7 and MDA-MB-231) using MTT assay, anti-metastatic assay, apoptotic screening by AO/EB staining and in vivo in N-Methyl-N-nitrosourea (MNU) induced breast carcinoma model. Sprague-Dawley rats with developed tumors (50 mg/kg MNU i.p.) were grouped in four, namely MNU control (0.25 % of CMC p.o.), standard group (doxorubicin 2 mg/kg once in 4 days, i.p.), C1 and C2 groups (50 mg/kg p.o. each). After 21 days of treatments, tumor volume and weight were assessed. Excised tumors were subjected to DNA fragmentation study. MTT assay showed IC50 values of 62.56 and 37.8 µM by for C1 and C2. Both compounds increased apoptotic bodies more than 3 fold compared to normal control in AO/EB staining. Antimetastatic (scratch wound) assay showed a significant (p<0.05) reduction in cell migration after 24 h and 48 h treatments compared to normal control. In in vivo studies, tumor weight and tumor volume were significantly (p<0.05) reduced in the doxorubicin group as well as in test groups compared to MNU control. DNA fragmentation assay showed an increase in the number of bands formed in C1 and C2 compared to normal control. Results obtained from in vitro and in vivo studies demonstrated the significant anticancer potentials of C1 and C2.

Synthesis, anticancer, structural, and computational docking studies of 3-benzylchroman-4-one derivatives.

A series of 3-Benzylchroman-4-ones were synthesized and screened for anticancer activity by MTT assay. The compounds were evaluated against two cancerous cell lines BT549 (human breast carcinoma), HeLa (human cervical carcinoma), and one noncancerous cell line vero (normal kidney epithelial cells). 3b was found to be the most active molecule against BT549 cells (IC50 = 20.1 µM) and 3h against HeLa cells (IC50 = 20.45 µM). 3b also exhibited moderate activity against HeLa cells (IC50 = 42.8 µM). The molecular structures of 3h and 3i were solved by single crystal X-ray crystallographic technique. Additionally, the molecular docking studies between the tumour suppressor protein p53 with the lead compound 3h, which exhibited better anticancer activity against HeLa cells was examined.

In Silico Drug-Designing Studies on Flavanoids as Anticolon Cancer Agents: Pharmacophore Mapping, Molecular Docking, and Monte Carlo Method-Based QSAR Modeling.

In silico molecular modeling studies were carried out on some newly synthesized flavanoid analogues. Search for potential targets for these compounds was performed using pharmacophore-mapping algorithm employing inverse screening of some representative compounds to a large set of pharmacophore models constructed from human target proteins. Further, molecular docking studies were carried out to assess binding affinity of these compounds to proteins mediating tumor growth. In vitro anticancer studies were carried out on colon cancer cell lines (HCT116) to assess validity of this approach for target identification of the new compounds. Further important structural features of compounds for anticolon cancer activity were assessed using Monte Carlo-based SMILES and hydrogen graph-Based QSAR studies. In conclusion this study have depicted successful and stepwise application of pharmacophore mapping, molecular docking, and QSAR studies in target identification and lead optimization of flavonoids.

Selected novel 5'-amino-2'-hydroxy-1, 3-diaryl-2-propen-1-ones arrest cell cycle of HCT-116 in G0/G1 phase.

A series of 5'-amino-2'-hydroxy-1,3-diaryl-2-propen-1-ones (AC1-AC15) were synthesized by Claisen-Schmidt condensation of 5'-acetamido-2'-hydroxy acetophenone with various substituted aromatic aldehydes. The synthesized compounds were characterized by FTIR, (1)H NMR and mass spectrometry and evaluated for their selective cytotoxicity using MTT assay on two cancer cell lines namely breast cancer cell line (MCF-7), colon cancer cell line (HCT-116) and one normal kidney epithelial cell line (Vero). Among the tested compounds, AC-10 showed maximum cytotoxic effect on MCF-7 cell line with IC50 value 74.7 ± 3.5 µM. On HCT-116 cells, AC-13 exhibited maximum cytotoxicity with IC50 value 42.1 ± 4.0 µM followed by AC-14 and AC-10 with IC50 values 62 ± 2.3 µM and 95.4 ± 1.7 µM respectively. All tested compounds were found to be safe on Vero cell line with IC50 value more than 200 µM. Based on their highest efficacy on HCT-116, AC-10, AC-13 and AC-14 were selected for mechanistic study on this cell line by evaluating changes nucleomorphological characteristics using acridine orange-ethidium bromide (AOEB) dual stain and by analyzing cell cycle with flow cytometry using propidium iodide stain. In AOEB staining, all three tested compounds showed significant (p < 0.05) increase in percentage apoptotic nuclei compared to control cells, with highest increase in apoptotic nuclei by AC-13 treatment (31 %). Flow cytometric studies showed cell cycle arrest by AC-10 and AC-14 treatment in G0/G1 phase and by AC-13 in G0/G1 and G2/M phase. The study reflected the potential of AC-10, AC-13 and AC-14 to be the lead molecules for further optimization.

rac-3-(4-Hy-droxy-benz-yl)chroman-4-one.

In the racemic title compound, C16H14O3, the ring of the 4-hy-droxy-benzyl substituent group forms a dihedral angle of 80.12 (12)° with the benzene ring of the chromanone system. Two C atoms of the pyran-one ring and the H atoms on the benzyl α-C atom are disordered over two sites, with site-occupation factors of 0.818 (8) and 0.182 (8). The crystal structure is stabilized by O-H⋯O hydrogen bonds, which form parallel one-dimensional zigzag chains down the c axis and are inter-connected by both methine C-H⋯O hydrogen bonds and weak aromatic C-H⋯π inter-actions, giving a sheet structure lying parallel to [011].

3-(3,4-Dimeth-oxy-benz-yl)chroman-4-one.

In the title compound, C(18)H(18)O(4), the six-membered chroman-4-one ring adopts an envelope conformation with the C atom bonded to the bridging CH(2) atom as the flap. The dihedral angle between the mean plane of the fused pyranone ring and the dimeth-oxy-substituted benzene ring is 89.72 (2)°. In the crystal, adjacent molecules are linked via C-H⋯π inter-actions.