Background: Quinolines have demonstrated various biological activities such as antimalarial, antibacterial and anticancer. Hence, compounds with such scaffold have been used as lead in drug development. This project is, therefore, aimed to synthesis and evaluates some biological activities of quinoline analogs.Methods: 2-Chloro-7-fluoroquinoline-3-carbaldehydes were synthesized by the application of Vilsmeier–Haack reaction. The chlorine in the fluoroquinoline-3-carbaldehyde was replaced with various nucleophiles. The aldehyde functional group was also converted to carboxylic acid and imine groups using oxidizing agent and various amines, respectively. The structures of the compounds synthesized were characterized by spectroscopic methods. Disc diffusion and DPPH assays were used to evaluate the antibacterial and antioxidant activities, respectively. The in silico molecular docking analysis of the synthesized compounds were done using AutoDock Vina againstE. coliDNA Gyrase B and human topoisomerase IIα. The drug likeness properties were assessed using SwissADME and PreADMET.Results: Nine novel quinoline derivatives were synthesized in good yields. The in vitro antibacterial activity of the synthesized compounds was beyond 9.3 mm inhibition zone (IZ). Compounds4,5,6,7,8,10,15, and16exhibited activity againstE. coli,P. aeruginosa,S. aureusandS. pyogeneswith IZ ranging from 7.3 ± 0.67 to 15.3 ± 0.33 mm at 200 μg/mL. Compound9displayed IZ against three of the bacterial strains exceptS. aureus. The IC₅₀for the radical scavenging activity of the synthesized compounds were from 5.31 to 16.71 μg/mL. The binding affinities of the synthesized compounds were from − 6.1 to − 7.2 kcal/mol againstE. coliDNA gyrase B and − 6.8 to − 7.4 kcal/mol against human topoisomerase IIα. All of the synthesized compounds obeyed Lipinski’s rule of five without violation.Conclusion: Compounds4,5,6,7,8,10,15, and16displayed activity against Gram positive and Gram negative bacterial strains indicating that these compounds might be used as broad spectrum bactericidal activity. Compound8(13.6 ± 0.22 mm) showed better IZ againstP. aeruginosacompared with ciprofloxacin (10.0 ± 0.45 mm) demonstrating the potential of this compound as antibacterial agent against this strain. Compounds5,6,7,8,9and10showed comparable binding affinities in their in silico molecular docking analysis againstE. coliDNA gyrase B. All of the synthesized compounds also obeyed Lipinski’s rule of five without violation which suggests these compounds as antibacterial agents for further study. Compounds7and8were proved to be a very potent radical scavenger with IC₅₀values of 5.31 and 5.41 μg/mL, respectively. Compound5,6,8,10and16had comparable binding affinity against human topoisomerase IIα suggesting these compounds as a possible candidate for anticancer drugs.

2-Chloroquinoline-3-carbaldehyde and 2-chloro-8-methylquinoline-3-carbaldehyde derivatives were synthesized through Vilsmeier formulation of acetanilide and N-(o-tolyl)acetamide. Aromatic nucleophilic substitution reaction was used to introduce various nucleophiles in place of chlorine under different reaction conditions. The carbaldehyde group was oxidized by permanganate method and reduced with metallic sodium in methanol and ethanol. The synthesized compounds were characterized by UV-Vis, IR, and NMR. The antibacterial activity of the synthesized compounds was screened against two Gram-positive bacteria (Bacillus subtilisATCC6633 andStaphylococcus aureusATCC25923) and two Gram-negative bacteria (Escherichia coliATCC 25922 andPseudomonas aeruginosaATCC 27853). Most of the compounds displayed potent activity against two or more bacterial strains. Among them, compounds6and15showed maximum activity againstPseudomonas aeruginosawith mean inhibition zones of 9.67 ± 1.11 and 10.00 ± 0.44 mm, respectively, while ciprofloxacin showed mean inhibition zone of 8.33 ± 0.44 mm at similar concentration. On the other hand, compound8exhibited maximum activity againstEscherichia coliwith inhibition zones of about 9.00 ± 0.55 mm at 300 μg/mL and 11.33 ± 1.11 mm at 500 μg/mL. The radical scavenging activity of these compounds was evaluated using 1,1-diphenyl-2-picryl hydrazyl (DPPH), and all of them displayed moderate antioxidant activity, with compound7exhibiting the strongest activity. The molecular docking study of the synthesized compounds was conducted to investigate their binding pattern with DNA gyrase, all of them were found to have minimum binding energy ranging from –6.0 to –7.33 kcal/mol, and the best result was achieved with compound11. The findings of the in vitro antibacterial and molecular docking analysis demonstrated that the synthesized compounds have potential of antibacterial activity and can be further optimized to serve as lead compounds.

Ocimum cufodontii((Lanza) A.J.Paton) has been traditionally used in Ethiopia against bacteria.The extracts of the leaves and roots ofO. cufodontiiafter silica gel column chromatography furnished compounds1–5, compounds3and4are new natural products. The oil from the hydro-distillation of the leaves, after analyzed with GC–MS, has led to the identification ofβ-caryophyllene as a principal component, suggesting the essential oil as medicine and spices to enhance the taste of food. The constituents ofO. cufodontiiwere assessed for their antibacterial activity againstE. coli, K. pneumonia, S. typhymuriumandS. aureus.The best activity was displayed againstS. aureusby the hexane extract of the roots, compound4, and the essential oil with an inhibition zone of 17, 15, and 19 mm, respectively. Molecular docking analysis revealed that compound1has better docking efficiency and forms hydrophobic interactions with five amino acids (ARG192, PHE196, GLU185, GLU193, and LYS189). This suggests that the compounds may act as potential inhibitors of DNA gyrase. The constituents were also assessed for their antioxidant activities using DPPH, ferric thicyanate and ferric reducing power assay. The hexane extracts of the roots inhibited the DPPH radical and peroxide formation by 90.5 and 83%, respectively, suggesting the potential of the extract as an antioxidant. Furthermore, the hexane extract of the roots ofO. cufodontiiexhibited the maximum reducing power compared with the EtOAc and methanol extracts. Hence, the activity displayed herein indicated as the plant has great potential as a remedy for diseases caused by bacteria and radicals.

4-Quinolone and its analogs are heterocyclic classes of organic compounds displaying biologically active and a broad spectrum of pharmaceutical drug scaffolds.

Vernonia amygdalina is traditionally used in Ethiopia to treat various diseases. This prompted us to isolate bioactive compounds from the flowers of this plant. The CHCl₃ extract after silica gel column chromatography has led to the isolation of two compounds identified as tricosane (1) and vernolide (2), while the acetone extract furnished isorhamnetin (3) and luteolin (4). The acetone extract and isorhamnetin significantly scavenged the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical by 91.6 and 94%, respectively. It was also shown that the acetone extract and isorhamnetin inhibited lipid peroxidation by 74 and 80%, respectively. The extracts and isolated compounds were also evaluated for their antibacterial activity with the CHCl₃ extract and vernolide showing strong activity against S. aureus with an inhibition zone of 21 and 19 mm, respectively. On the other hand, the acetone extract and isorhamnetin were active against all bacterial pathogens tested. The work presented herein has demonstrated that vernolide and isorhamnetin had antibacterial activity. The antioxidant activity displayed by the flowers of V. amygdalina is accounted to the presence of isorhamnetin. Therefore, the biological activities displayed by the extracts and isolated compounds from this plant corroborate the traditional uses of this plant by the local people against various diseases.

Background: Cucumis prophetarumis traditionally used to treat liver and lung disorders, heart failure, diarrhea, gonorrhea, skin infections, intestinal problems and cancer. In the present work, the isolation of two novel compounds along with their antibacterial and antioxidant activities is reported for the first time.Methods: Silica gel column chromatography was applied to separate constituents of the roots ofC. prophetarum.The structures of isolated compounds were established using¹H NMR,¹³C NMR, DEPT-135, COSY, HSQC and HMBC. Agar well diffusion, DPPH assay and ferric thiocyante methods were used for antibacterial, radical scavenging and anti-lipid peroxidation activities, respectively. AutoDock Vina open source program was used for molecular docking analysis.Results: Evaluation of the in vitro antibacterial activity of the constituents againstS. aureus, B. subtilis, E. coliandS. thyphimuriumrevealed that the hexane extract were active againstE. coliwith IZ of 15.0 ± 1.41 mm, whereas an IZ of 14.6 ± 1.70 mm for MeOH extract was observed againstS. aureus. Compound1displayed IZ of 13.6 ± 0.94 mm againstE. coliand curcurbiatin2showed activity againstB. subtiliswith IZ of 13.3 ± 0.54 mm. The molecular docking analysis showed that cucurbitacins2and3have binding energy of -6.7 and -6.9 kcal/mol, respectively. The methanol and the hexane extracts of the roots ofC. prophetaruminhibited DPPH radical by 70.4 and 63.3% at 100 µg/mL, respectively. On the other hand, the methanol extract inhibited lipid peroxidation by 53.0%.Conclusion: The present study identified five compounds from the root extracts ofC. prophetarum, of which two are novel cucurbitacins (1,2). The in vitro antibacterial activity of the hexane and methanol extracts was better than the activity displayed by the isolated compounds. This is probably due to the synergistic effects of the constituents present in the root extract. The in silico molecular docking study results showed that, compounds2and3have minimum binding energy and have good affinity toward the active pocket, thus, they may be considered as good inhibitor of DNA gyrase B. Furthermore, the “drug-likeness” and ADMET prediction of compounds2–5nearly showed compliance with the Lipinski rule, with good absorption, distribution, metabolism, and excretion generally. The radical scavenging and anti-lipid peroxidation activities of the extracts were better than the isolated compounds. This is attributed to the presence of phenolics and flavonoids as minor constituents in the extracts of these species. Therefore, the in vitro antibacterial activity and molecular docking analysis suggest the potential use of the isolated compounds as medicine which corroborates the traditional use of the roots ofC. prophetarum.