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Background: Cancer is one of the leading causes of mortality globally. To cope with cancer, it is necessary to develop anticancer drugs. Bioactive natural products, i.e. diarylheptanoids, have gained significant attention of researchers owing to their intriguing structures and potent biological activities. In this article, considering the development of anticancer drugs with enhanced selectivity towards cancerous cells, a series of Cyclic Diarylheptanoids (CDHs) are designed, synthesized and evaluated their biological activity. Objective: To establish an easy route for the synthesis of diarylheptanoids, and evaluate their antiproliferative, and topoisomerase-I &-IIα inhibitory activities, for developing potential anticancer drugs among CDHs. Methods: Diarylheptanoids were synthesized from reported linear diarylheptanoids using the classical Ullmann reaction. Antibacterial activity was evaluated by the filter paper disc diffusion method. Cell viability was assessed by measuring mitochondrial dehydrogenase activity with a Cell Counting Kit (CCK-8). Topoisomerases I and II (topo-I and -IIα) inhibitory activity was measured by the assessment of relaxation of supercoiled pBR322 plasmid DNA. IFD protocol of Schrodinger Maestro v11.1 was used to characterize the binding pattern of studied compounds with the ATPase domain of the human topo-IIα. Results: The synthesized CDHs were evaluated for their biological activities (antibacterial, antiproliferative, and topoisomerase-I & -IIα inhibitory activities, respectively). Leading to obtain a series of anticancer agents with the least inhibitory activities against different microbes, improving their selectivity for cancer cells. In brief, most of the synthesized CDHs had excellent antiproliferative activity against T47D (human breast cancer cell line). Pterocarine possessed the strongest activity (2i; IC50 = 0.63µM) against T47D. The cyclic diarylheptanoid 2b induced 30% inhibition of topoisomerase-IIα activity at 100μM compared with the reference of etoposide, which induced 72% inhibition. Among the tested compounds, galeon (2h) displayed very low activity against four bacterial strains. Compounds 2b, 2h, and 2i formed hydrogen bonds with Thr215, Asn91, Asn120, Ala167, Lys168 and Ile141 residues, which are important for binding of ligand compound to the ATPase binding site of topoisomerase IIα by acting as ATP competitive molecule validated by docking study. In silico Absorption, Distribution, Metabolism and Excretion (ADME) analysis revealed the predicted ADME parameters of the studied compounds which showed recommended values. Conclusion: A series of CDHs were synthesized and evaluated for their antibacterial, antiproliferative, and topo-I & -IIα inhibitory activities. SARs study, molecular docking study and in silico ADME analysis were conducted. Five compounds exhibited excellent and selective antiproliferative activity against the human breast cancer cell line (T47D). Among them, a compound 2h showed topo-IIα activity by 30% at 100µM, which represented a moderate intensity of inhibition compared with etoposide. Three of them formed hydrogen bonds with Thr215, Asn91, Asn120, and Ala167 residues, which are considered as crucial residues for binding to the ATPase domain of topoisomerase IIα. According to in silico drug-likeness property analysis, three compounds are expected to show superiority over etoposide in case of absorption, distribution, metabolism and excretion.

Abstract:The Friedländer reactions of acetylbenzenes and 2-acetylpyridine with 3-aminonaphthalene-2-carbaldehyde afforded the corresponding 2-phenylbenzo[g]quinoline and 2-(pyrid-2-yl)benzo[g]quinoline, respectively. The same reactions of 3-aminonaphthalene-2-carbaldehyde with 1,2-, 1,3-, 1,4-di-and 1,3,5-triacetylbenzenes, however, afforded a series of corresponding (benzo[g]quinolin-2-yl)benzenes as new N,C-bidentate and unexpected benzo[g]quinoline. Crystallinity, thermal properties, absorption and emission spectral properties of the products were studied.

Corona Virus Disease (COVID-19) is announced as pandemic by World Health Organization (WHO) since 11th March 2020. Riau Province has many herbal plants e.g. Cheilocostus specious, Euphorbia hirta l, Cassia torra, Bryophyllum pinnatum, Daniella ensifollia, and Ziziphus mauritiana that can cure many diseases and there is not report yet focusing on in-silico method using SARS-CoV-2 protease (PDB ID:6LU7). This study aims to reveal the potential of compounds contained in Riau Herbal Plants as anti SARS-CoV-2 through its binding to protein receptors. The study was conducted by molecular docking using Autodock Vina 1.5.6 and drug ability studies using Swiss ADME. The docking results of six active compounds including diosgenin, tannin, triterpenoid, chrysophanol, flavone and phytosterol were -8,3; -7,5; -7,5; -7,2; -6,9; -6,9 respectively against the affinity result for natural ligand of COVID-19 (-6,1). This result indicates the stronger bond between ACE2 and inhibitors because the affinity value of active compounds are higher than natural ligand of COVID-19. The SwissADME results show that triterpenoid and tannin violate some Lipinski Rules that make their drug-likeness is low. In general, all the active compounds were potential as candidates of SARS-CoV-2 antiviral but the most potential one is diosgenin in Cheilocostus specious.

Chemistry of 1,10-phenanthroline has long been of interest since first synthesis in 1898. 1 The importance of 1,10phenanthroline and its substituted analogues stems from their metal chelating properties and such ability has been widely applied in analytical chemistry for the analysis of metal cationic species. 2 The 1,10-phenanthroline moiety has been used not only as a single molecule but also as a part of macrocyclic ligand systems for molecular recognition, 3 cleavage of nucleic acids, 4 sensing agents, 5 catalysis for chemical reaction, 6 and photolysis, 7 and as therapeutic and bioanalytical applications, 8 which have been compiled in several reviews. 9 As the dimeric and cyclic 1,10-phenanthrolines are concerned, 2,2 0 -azabis(1,10-phenanthroline) (1b), 10 2,2 0 -thiobis(1,10-phenanthroline) (1c), 11 1,3(2,9)-diphenanthrolinacyclobutaphane (2a), 12 2,4-diaza-1,3(2,9)-diphenanthrolinacyclobutaphane (2b), 13 and 2,4-dithia-1,3(2,9)-diphenanthrolinacyclobutaphane (2c) 11c,14 were reported and have been attractive in variety of areas. 9c,10c,11c,13a,c However carbon-bridged di(1,10-phenanthrolin-2-yl)methane (1a) and the oxa-bridged 2,2 0 -oxybis (1,10-phenanthroline) (1d) and 2,4-dioxa-1,3(2,9)diphenanthrolinacyclobutaphane (2d), have not been reported. We herein described the preparation and properties of two new 1,10phenanthroline ethers, namely, 2,2 0 -oxybis(1,10-phenanthroline) (1d) and 2,4-dioxa-1,3(2,9)-diphenanthrolinacyclobutaphane (2d).Initial attempt for the synthesis of 1d involved a reaction of 1,10-phenanthrolin-2(1H)-one (3a) 15 and 2-chloro-1,10phenanthroline (4a) 16 in presence of KOH under the same condition for 1c. 11a,b The 1 H NMR spectrum of the product showed that it consisted of a mixture of 1d and 3a in a ratio of 1:4. To explain increased amount of 3a, we repeated the reaction with more reactive 2-bromo-1,10-phenanthroline 17 to give a 1.1:1 mixture of 1d and 3a. Formation of the same hydrolysis product, 3a, has also been reported in the reaction of 4a with 3c 18 reflecting that the low reactivity of 1a towards nucleophilic substitution and/or weak acidity of the amide proton of 3a might induce hydroxylation of 4a before it can undergo nucleophilic attack by the enolate anion. 19 Therefore, we used NaH to deprotonate 3a and the resulting enolate anion was then treated with excess of 4a, which led to 1d in 75% yield with a trace (7%) amount of 4a. 20 The 13 C NMR spectra of 1d showed resonances at δ 158.5 ppm for C2, which is comparable to those for C2 in 2c (δ 156.8) and in 3c (δ 181.0) 11a in CDCl 3 .For the preparation of cyclic diether 2d, 9-chloro-1,10phenanthrolin-2(1H)-one (3b) can be a good starting material, which can be prepared by hydrolysis of 2,9-dichloro-1,10-phenanthroline (4b) 13a with 36% (w/w) aqueous HCl. 21 The same reaction condition described above for 1d was applied to 3b to yield 2d in 44% yield. 22 1 H NMR spectrum of 2d showed two doublets at δ 8.00 and 6.65 (J = 9.5 Hz) for H3 and H4, respectively, and a singlet at δ 7.46 for H5, while 13 C NMR spectrum sho...