Synthesis of Some New Fluorinated Hexahydroquinoline and Acridinedione Derivatives in Trifluoroethanol

This article describes one-pot synthesis of new fluorinated hexahydroquinoline derivatives via unsymmetric Hantzsch reaction involving 5-trifluoromethyl-1,3-cyclohexanedione, aldehydes, acetoacetate ester, and ammonium acetate in trifluoroethanol (TFE). The reaction is simple and rapid with high yield

5,7-Dibromo-3-trifluoro­methyl-3,4-dihydro­acridin-1(2H)-one

In the title compound, C14H8Br2F3NO, the mol­ecule is disordered across an approximate non-crystallographic mirror plane, which is in the plane of the fused ring system [The tetrahedral C atom bearing the trifluormethyl substituent is disordered with site occupancy factors of 0.80 (2) and 0.20 (2)]. In the crystal, a one-dimensional stacking of mol­ecules involves inter­actions between the pyridine ring and symmetry-related Br and O atoms of adjacent mol­ecules. The stacking distance between the mean planes of adjacent mol­ecules is 3.395 (4) Å

Novel trifluoromethylated 9-amino-3,4-dihydroacridin-1(2H)-ones act as covalent poisons of human topoisomerase IIα

A number of topoisomerase II-targeted anticancer drugs, including amsacrine, utilize an acridine or related aromatic core as a scaffold. Therefore, to further explore the potential of acridine-related compounds to act as topoisomerase II poisons, we synthesized a series of novel trifluoromethylated 9-amino-3,4-dihydroacridin-1(2H)-one derivatives and examined their ability to enhance DNA cleavage mediated by human topoisomerase IIα. Derivatives containing a H, Cl, F, and Br at C7 enhanced enzyme-mediated double-stranded DNA cleavage ∼5.5- to 8.5-fold over baseline, but were less potent than amsacrine. The inclusion of an amino group at C9 was critical for activity. The compounds lost their activity against topoisomerase IIα in the presence of a reducing agent, displayed no activity against the catalytic core of topoisomerase IIα, and inhibited DNA cleavage when incubated with the enzyme prior to the addition of DNA. These findings strongly suggest that the compounds act as covalent, rather than interfacial, topoisomerase II poisons

In vitro anticancer screening of 24 locally used Nigerian medicinal plants

Background Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 μg/ml. Conclusions Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway

In vitro Anticancer Screening of 24 Locally Used Nigerian Medicinal Plants

Background: Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity. Methods: The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines. Results: Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma cell lines. Erythrophleum suaveolens (Guill. & Perr.) Brenan was found to demonstrate potent anti-cancer activity in this study exhibiting IC50 = 0.2-1.3 $\mu$g/ml. Conclusions: Based on the significantly potent activity of some plants extracts reported here, further studies aimed at mechanism elucidation and bio-guided isolation of active anticancer compounds is currently underway.Chemistry and Chemical Biolog

A Mini Review of Novel Topoisomerase II Inhibitors as Future Anticancer Agents

Several reviews of inhibitors of topoisomerase II have been published, covering research before 2018. Therefore, this review is focused primarily on more recent publications with relevant points from the earlier literature. Topoisomerase II is an established target for anticancer drugs, which are further subdivided into poisons and catalytic inhibitors. While most of the topoisomerase II-based drugs in clinical use are mostly topoisomerase II poisons, their mechanism of action has posed severe concern due to DNA damaging potential, including the development of multi-drug resistance. As a result, we are beginning to see a gradual paradigm shift towards non-DNA damaging agents, such as the lesser studied topoisomerase II catalytic inhibitors. In addition, this review describes some novel selective catalytic topoisomerase II inhibitors. The ultimate goal is to bring researchers up to speed by curating and delineating new scaffolds as the leads for the optimization and development of new potent, safe, and selective agents for the treatment of cancer

Inflow of Foreign Direct Investment (Fdi) and Management Approaches of Multinationals in Nigeria

The study investigated the implication of foreign direct investment flows in the prevalence of management approaches in thirty multinational organizations in Nigeria. The multivariate regression analysis was employed for the identification of factors in the Nigeria investment environment (other than fiscal performance) that may have strong mediating impact. Results from the analysis showed that the predominant staffing strategy in most multinational organizations with FDI presence skew to polycentric (β = 0.28; p < 0.05) staffing approach more than to ethnocentric (β = 0.03; p < 0.05). This can be explained by the prevalence of host country staffers occupying strategic position in host country’s offices. Manager’s perception of employee effectiveness is largely influenced by the employee level of aptitude and the employee tacit personality traits

Inflow of Foreign Direct Investment (Fdi) and Management Approaches of Multinationals in Nigeria

The study investigated the implication of foreign direct investment flows in the prevalence of management approaches in thirty multinational organizations in Nigeria. The multivariate regression analysis was employed for the identification of factors in the Nigeria investment environment (other than fiscal performance) that may have strong mediating impact. Results from the analysis showed that the predominant staffing strategy in most multinational organizations with FDI presence skew to polycentric (β = 0.28; p < 0.05) staffing approach more than to ethnocentric (β = 0.03; p < 0.05). This can be explained by the prevalence of host country staffers occupying strategic position in host country’s offices. Manager’s perception of employee effectiveness is largely influenced by the employee level of aptitude and the employee tacit personality traits

Diversity ideology: cultural festivals and fusion of diverse socio-ethnic construct, interest and ethnic cooperation

Cultural festivals as celebrated in Nigeria have enormous potential to drive fusion of diverse socio-ethnic construct. Our study focused on only three psychometric rationales or premise for evaluating common preference in cultural mixes. Fundamentally each ethnic group in Nigeria feels strong about the uniqueness of their culture. Distinct cultural traditions have been preserved and appreciated over history. We synthesized this construct at α = 0.05. Among others, key factors of multiculturalism (r = 0.39) (ideological condition that believe tradition must not be altered or acculturated) such as cuisines, costumes, rituals, languages did not significantly encourage fusion of socio-ethnic groups. Furthermore, among others, key factors of colorblindness (r = 0.52) (ideological condition that believe that culture has common origin “human beings” and common goals “satisfy human’s needs and desires”; and so people everywhere can bridge cultural differentia) such as local business, heritage site, Lifestyle, security correlates. However, lifestyle and security mediates in certain domains of cultural consumption that evokes fear of cultural mixing and which does not absolutely change ethnic predominant cultural mindset. Key factors of polyculturalism (r = 0.79)  (ideological condition with the believe that traditions and perspectives influence each other as cultural groups continually make contact and interact) such as awareness, values, friendliness and markets appeared significant in driving fusion. Multiculturalism (p < 0.05) offers high propensity to increasing preference for cultural fusion options through increasing concerns about the impurity from the mixing elements of different socio-ethnic grou

Diversity ideology: cultural festivals and fusion of diverse socio-ethnic construct, interest and ethnic cooperation

Cultural festivals as celebrated in Nigeria have enormous potential to drive fusion of diverse socio-ethnic construct. Our study focused on only three psychometric rationales or premise for evaluating common preference in cultural mixes. Fundamentally each ethnic group in Nigeria feels strong about the uniqueness of their culture. Distinct cultural traditions have been preserved and appreciated over history. We synthesized this construct at α = 0.05. Among others, key factors of multiculturalism (r = 0.39) (ideological condition that believe tradition must not be altered or acculturated) such as cuisines, costumes, rituals, languages did not significantly encourage fusion of socio-ethnic groups. Furthermore, among others, key factors of colorblindness (r = 0.52) (ideological condition that believe that culture has common origin “human beings” and common goals “satisfy human’s needs and desires”; and so people everywhere can bridge cultural differentia) such as local business, heritage site, Lifestyle, security correlates. However, lifestyle and security mediates in certain domains of cultural consumption that evokes fear of cultural mixing and which does not absolutely change ethnic predominant cultural mindset. Key factors of polyculturalism (r = 0.79)  (ideological condition with the believe that traditions and perspectives influence each other as cultural groups continually make contact and interact) such as awareness, values, friendliness and markets appeared significant in driving fusion. Multiculturalism (p < 0.05) offers high propensity to increasing preference for cultural fusion options through increasing concerns about the impurity from the mixing elements of different socio-ethnic grou