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Modeling of Quinoacridinium Derivatives as Antitumor Agents using a QSAR analysis Hadanu, Ruslin
Indonesian Journal of Pharmacy Vol 30 No 3, 2019
Publisher : Faculty of Pharmacy Universitas Gadjah Mada, Yogyakarta, Skip Utara, 55281, Indonesia

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (939.229 KB) | DOI: 10.14499/indonesianjpharm30iss3pp167

Abstract

A QSAR analysis has been performed on a compound series of 1-11 quinoacridinium derivatives as internal test compounds, and compounds of 12-15 quinoacridinium derivatives as external test compounds. The electronic descriptors used in this study were atomic net charge (q), dipole moment (μ), ELUMO, EHOMO, polarizability (α), and Log P. They were calculated through HyperChem for Windows 8.0 software using semi-empirical PM3 method. The antitumor activity (IC50) of quinoacridinium derivative compounds was obtained from literature. Furthermore, the model of QSAR equation was analyzed through RML method which produced the best QSAR equation model: Log IC50 = -13.010 + 15.338(qC3) - 4.31(qC4) - 155.308(qC9) + 33.626(qC11) + 26.626(qC12) + 24.631(qC14) - 0.228(μ) - 0.621(ELUMO) - 0.066(α) + 0.233(Log P). The model of QSAR equation has a correlation coefficient n = 11, (r) = 1.00, (r2) = 1.00, SE = 0, and PRESS = 0.003. Among 28 compounds of quinoacridinium derivative which were designed, only 15 compounds, namely 16, 19-20, 22-28, 30-32, 39, and 40 compounds, have been recommended to be synthesized in the laboratory.
Synthesis and Antimalarial Activity of 2-Phenyl-1,10-Phenanthroline Derivative Compounds Hadanu, Ruslin; Mustofa, Mustofa; Nazudin, Nazudin
Jurnal Natur Indonesia Vol 15, No 1 (2013)
Publisher : Lembaga Penelitian dan Pengabdian kepada Masyarakat Universitas Riau

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (136.973 KB) | DOI: 10.31258/jnat.15.1.57-62

Abstract

To develop new potential antimalarial drugs of 2-phenyl-1,10-phenanthroline 5 derivatives from 8-aminoquinoline as startingmaterial were synthesized in good yields. The synthesis of 2-phenyl-1,10-phenanthroline 5 derivatives compoundswith 8-aminoquinoline 4 as starting material through three steps has been carried out. The first step of reactions is aldolcondensation of benzaldehyde 1 with acetaldehyde 2. The result of reactions is cinnamaldehyde 3 (92.14%) in the form ofyellow solid. The second step of reactions was synthesized of 2-phenyl-1,10-phenanthroline 5 (brown solid, 54.63%)through cyclization of 8-aminoquinoline 4 with cinnamaldehyde 3 compound. The third step of reactions is methylation andethylation of 2-phenyl-1,10-phenanthroline using dimethyl sulphate (DMS) and diethyl sulphate (DES) reagents that it wasrefluxed for 17 and 19 h, respectively. The results of reactions are (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6and (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 in yield from 90.62% and 89.70%, respectively. The results oftesting in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate 7 compound has higherantimalarial activity (IC 50 :0.13 ± 0.02 μM) than antimalarial activity of (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate6 compound (IC 50 :0.25 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :2.45 ± 0.09 μM). While, the resultsof testing in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum D10 strain to 2-phenyl-1,10-phenanthroline 5 derivatives obtained that (1)-N-methyl-9-phenyl-1,10-phenanthrolinium sulphate 6 compound has higherantimalarial activity (IC 50 :0.10± 0.04 μM) than antimalarial activity of (1)-N-ethyl-9-phenyl-1,10-phenanthrolinium sulphate7 (IC 50 :0.18 ± 0.01 μM) and 2-phenyl-1,10-phenanthroline 5 compound (IC 50 :0.55 ± 0.07 μM).
SINTESIS SENYAWA T-KALKON BAHAN DASAR SENYAWA TABIR SURYA Hadanu, Ruslin
Molluca Journal of Chemistry Education (MJoCE) Vol 8 No 1 (2018): Molluca Journal of Chemistry Education (MJoCE)
Publisher : Prodi Pendidikan Kimia FKIP Universitas Pattimura

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30598/MJoCEvol8iss1pp36-41

Abstract

A novel method for the synthesis of t-chalcone as material start of sunscreen compounds through aldol condensation reaction was introduced using NaOH/EtOH as a catalyst and solvent. The structures of the t-chalcone of product were confirmed by IR, GC-MS and 1H-NMR spectrosfotometer
In vitro anticancer activity of N-benzyl 1,10-phenanthroline derivatives on human cancer cell lines and their selectivity Eti Nurwening Sholikhah; Jumina Jumina; Sitarina Widyarini; Ruslin Hadanu; Mustofa Mustofa
Indonesian Journal of Biotechnology Vol 23, No 2 (2018)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.22146/ijbiotech.33997

Abstract

This research was conducted to evaluate the anticancer activity of new compounds of benzyl-1,10- phenanthroline derivatives and their selectivity. In vitro anticancer activity of 11 benzyl-1,10-phenanthroline derivatives were conducted on three human cancer cell lines, cervical cancer (HeLa), myeloma (NS-1), and breast cancer (MCF-7) using MTT-based cytotoxicity assay. The cytotoxicity of each compound was assessed to normal Vero cell line by the same method. The in vitro anticancer activity and cytotoxicity was expressed by the concentration inhibiting 50% of the cell growth (IC50), and the selectivity index (SI) was determined by calculating ratio of the IC50 on Vero cell line and the human cancer cell lines. The results showed that among the 11 compounds tested, the (1)-N-(4-butoxybenzyl)-1,10-phenanthrolinium bromide exhibited the best in vitro anticancer activity with an IC50 27.60 ± 2.76 µM on HeLa, 6.42 ± 5.53 µM on NS-1 and 9.44 ± 2.17 µM on MCF-7 cell lines. Its SI were 377.65 ± 39.97 on HeLa, 6158.72 ± 5306.34 on NS-1 and 1140.11 ± 261.85 on MCF-7 cell lines. This study demonstrated that (1)-N-(4-butoxybenzyl)-1,10-phenanthrolinium bromide possessed a potential in vitro anticancer activity on cancer cell lines with high selectivity
SINTESIS DAN UJI AKTIVITAS SENYAWA (1)-N-(n-BUTIL)- DAN (1)-N-(t-BUTIL)-1,10-FENANTROLINIUM SEBAGAI SENYAWA POTENSIAL ANTIMALARIA BARU Ruslin Hadanu; Sabirin Mastjeh; Mustafa Mustafa; Eti Nurwening Sholikhah; Mahardika Agus Wijayanti
Molluca Journal of Chemistry Education (MJoCE) Vol 1 No 1 (2011): Molluca Journal of Chemistry Education (MJoCE)
Publisher : Program Studi Pendidikan Kimia FKIP Universitas Pattimura

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30598/MJoCEvol1iss1pp45-53

Abstract

The synthesis of (1)-N-(n- buthyl)- dan (1)-N-(t-buthyl)-1,10-phenanthrolinium with 1,10-phenanthroline monohydrate as starting material through two steps has been carried out. The first step of reaction is chlorination and bromination of n-buthyl-alcohol/t-buthyl alcohol using HCl and HBr, respectively. The result of reaction is nbuthyl bromide 2 (colourless liquid, 70.92%) and t-buthyl chloride 4 (colourless liquid, 92.36%), respectively. The second step of reaction is alkylation of 1,10-phenanthroline 5 using n-buthyl bromide and t-buthyl chloride reagents that its was refluxed for 21 and 23 h, respectively. The results of reaction are (1)-N-(n- buthyl)-1,10fenantrolinium bromida 6 and (1)-n-(t-buthyl)-1,10-fenantrolinium chloride 7 in yield from 84.70% and 78.16%, respectively. The results of testing in in vitro antiplasmodial activity at chloroquine-resistant P. falciparum FCR3 strain to (1)-N-(n-buthyl)- and (1)-N-(t-buthyl)-1,10- phenanthrolinium obtained that (1)-N-(n-buthyl)-1,10phenanthrolinium bromide 6 has higher antimalarial activity (IC50 : 0.03±0.01 µM) than antimalarial activity of (1)-n-(t-buthyl)-1,10-phenanthrolinium chloride 7 (IC50 : 2.09±0.08 µM). While, the results of testing in in vitro antiplasmodial activity at chloroquine-resistant P. falciparum D10 strain to (1)-N-(n-buthyl)- and (1)-N-(t-buthyl)1,10-f phenanthrolinium obtained that (1)-N-(n-butil)-1,10- phenanthrolinium bromide 6 has higher antimalarial activity (IC50 : 1.40±0.82 µM) than antimalarial activity of (1)-n-(t-buthyl)-1,10- phenanthrolinium chloride 7 (IC50 : 2.24±0.05 µM
SINTESIS DAN UJI AKTIVITAS ANTIMALARIA SENYAWA (1)-N-BENZIL-1,10- FENANTROLINIUM BROMIDA Ruslin Hadanu; Sabirin Mastjeh; Jumina Jumina; Mustafa Mustafa; Eti Nurwening Sholikhah; Mahardika Agus Wijayanti
Molluca Journal of Chemistry Education (MJoCE) Vol 1 No 2 (2011): Molluca Journal of Chemistry Education (MJoCE)
Publisher : Program Studi Pendidikan Kimia FKIP Universitas Pattimura

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30598/MJoCEvol1iss2pp92-102

Abstract

A synthetic methods was employed to prepare (1)-N-benzyl)-1,10-phenanthroliniumbromide 4 from 1,10phenanthroline 3 and benzylchloride 1 through substitution and alkylation reactions. The compound (1)-Nbenzyl)-1,10-phenanthroliniumbromide 4 was tested through antiplasmodial test. The benzylbromide 2 was synthesized through substitution reaction of benzylchloride 1 and NaBr which has a yield of 74.25%. The (1)-N-benzyl)-1,10-phenanthroliniumbromide 4 was synthesized from 1,10-phenanthroline 3 using benzylbromide 2 reagents which refluxed for 8 hours with 84.04% yields. The results of testing in in vitro antiplasmodial activity at chloroquine-resistant Plasmodium falciparum FCR3 strain to (1)-N-benzyl)-1,10- phenanthroliniumbromide 4 has high antimalarial activity (IC50 : 0.10±0.04 µM)
SINTESIS SENYAWA t-KALKON BAHAN DASAR SENYAWA TABIR SURYA Ruslin Hadanu
Molluca Journal of Chemistry Education (MJoCE) Vol 8 No 1 (2018): Molluca Journal of Chemistry Education (MJoCE)
Publisher : Program Studi Pendidikan Kimia FKIP Universitas Pattimura

Show Abstract | Download Original | Original Source | Check in Google Scholar | DOI: 10.30598/MJoCEvol8iss1pp36-41

Abstract

A novel method for the synthesis of t-chalcone as material start of sunscreen compounds through aldol condensation reaction was introduced using NaOH/EtOH as a catalyst and solvent. The structures of the t-chalcone of product were confirmed by IR, GC-MS and 1H-NMR spectrosfotometer
Sintesis dan Uji Aktivitas Antimalaria Senyawa Turunan 2,4-Difenil-1,10-Fenantrolin RUSLIN HADANU; MUSTAFA MUSTAFA; NAZUDIN NAZUDIN
JURNAL ILMU KEFARMASIAN INDONESIA Vol 10 No 1 (2012): JIFI
Publisher : Fakultas Farmasi Universitas Pancasila

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (2003.906 KB)

Abstract

Malaria is still the main health problems in subtropical and tropical countries. There are 105 countries in the world at malaria endemic and more than 500 million cases or more than 2.7 million deaths from malaria each year. The traditional remedies are no longer effective and the incidence of malarial by P. falciparum, the most dangerous species of parasite, continues to grow, while some traditional drugs such as chloroquine has been resistance. Synthesis of 2,4-diphenyl-1,10-phenanthroline [5] compounds with benzaldehyde [1], acetophenone [2], t-calcone [3], 8-aminoquinoline [4] as starting material through three steps has been carried out. The results of all steps of the reaction were obtained compounds of [5], (1)-N methyl-7,9-diphenyl-1,10-phenanthrolinium sulfate [6] and (1)-N-ethyl-7,9-diphenyl-1,10-phenanthrolinium sulfate [7]. The results of antiplasmodial activity in vitro testing of the derivatives on chloroquine resistant P. falciparum FCR3 indicated that compound [7] has higher antimalarial activity (IC5O = 0.06±0.05 µM) than the activity of [6] compound (ICSO = 1.27±O.97 µM) and [5] compound (1C50 = 1.66±0.70 µM). Results of similar in vitro testing on chloroquine resistant P. falciparum D10 strain indicated that [7] compound has higher antimalarial activity (IC50 = 0.04±0.04 uM) than the activity of [5] compound (IC50 = 1.13±0.30 µM) and [6] compound (ICSO = 0.81±0.06 µM).
QSAR Analysis of Benzothiazole Derivatives of Antimalarial Compounds Based On AM1 Semi-Empirical Method Ruslin Hadanu; Salim Idris; I Wayan Sutapa
Indonesian Journal of Chemistry Vol 15, No 1 (2015)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (283.279 KB) | DOI: 10.22146/ijc.21228

Abstract

Quantitative Structure and Activity Relationship (QSAR) analysis of 13 benzothiazoles derivatives compound as antimalarial compounds have been performed using electronic descriptor of the atomic net charges (q), dipole moment (μ), ELUMO, EHOMO and polarizability (α). The electronic structures as descriptors were calculated through HyperChem for Windows 7.0 using AM1 semi-empirical method. The descriptors were obtained through molecules modeling to get the most stable structure after geometry optimization step. The antimalarial activity (IC50) were taken from literature. The best model of QSAR model was determined by multiple linear regression approach and giving equation of QSAR: Log IC50 = 23.527 + 4.024 (qC4) + 273.416 (qC5) + 141.663 (qC6) – 0.567 (ELUMO) – 3.878 (EHOMO)– 2.096 (α). The equation was significant on the 95% level with statistical parameters: n = 13, r = 0.994, r2 = 0.987, SE = 0.094, Fcalc/Ftable = 11.212, and gave the PRESS = 0.348. Its means that there were only a relatively few deviations between the experimental and theoretical data of antimalarial activity.
SYNTHESIS AND ANTIPLASMODIAL ACTIVITY TESTING OF (1)-N-ALKYL- AND (1)-N-BENZYL-6-NITRO-1,10-PHENANTHROLINIUM SALTS AS NEW POTENTIAL ANTIMALARIAL AGENTS Ruslin Hadanu; Sabirin Mastjeh; Jumina Jumina; Mustofa Mustofa; Eti Nurwening Sholikhah; Mahardika Agus Wijayanti
Indonesian Journal of Chemistry Vol 12, No 2 (2012)
Publisher : Universitas Gadjah Mada

Show Abstract | Download Original | Original Source | Check in Google Scholar | Full PDF (799.561 KB) | DOI: 10.22146/ijc.21356

Abstract

The synthesis of 5-nitro-1,10-phenanthroline hydrate 2 derivatives from 1,10-phenanthroline monohydrate as starting material has been carried out. The 5-nitro-1,10-phenanthroline hydrate 2 was obtained through nitration reaction using H2SO4 and HNO3 as catalyst and reagent, respectively. Synthesis of (1)-N-alkyl-6-nitro- and (1)-N-benzyl-6-nitro-1,10-phenanthrolinium have been prepared using dimethyl sulphate (DMS), diethyl sulphate (DES), benzyl chloride, benzyl bromine, and benzyl iodide. The reagents of benzyl bromine, and benzyl iodide were synthesized from benzyl chloride using NaBr in ethanol absolute and NaI in acetone, respectively. The five compounds of 5-nitro-1,10-phenanthroline hydrate 2 derivatives were conducted to evaluate the in vitro antiplasmodial activity. The in vitro antiplasmodial was evaluated on strains of Plasmodium falciparum FCR-3 resistant chloroquine and D10 sensitive chloroquine. The 50% inhibition concentration (IC50) of the five compounds ranged from 2.41±1.41 to 0.07±0.01 μM. The results showed that the (1)-N-benzyl-6-nitro-1,10-phenanthrolinium iodide had highest antiplasmodial activity.