Open Journal of Medicinal Chemistry

Journal Information
ISSN / EISSN : 2164-3121 / 2164-313X
Published by: Scientific Research Publishing, Inc. (10.4236)
Total articles ≅ 75
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Edward C. Lisic, Sarah N. Grossarth, Sarah B. Bowman, Jessica L. Hill, Michael W. Beck, Joseph E. Deweese, Xiaohua Jiang
Open Journal of Medicinal Chemistry, Volume 12, pp 1-13; https://doi.org/10.4236/ojmc.2022.121001

Abstract:
The new ligand, 2-acetylpyrazine-tertbutylthiosemicarbazone (APZ-tBTSC), and its Cu(II), Pd(II) and Pt(II) complexes have been synthesized. This ligand coordinates to the metal ions in a tridentate monoanionic fashion forming monometallic complexes with the formula [M(APZ-tBTSC)Cl]. The ligand and the three metal complexes [Cu(APZ-tBTSC)Cl], [Pd(APZ-tBTSC)Cl], and [Pt(APZ-tBTSC)Cl] were tested for anti-proliferative biological behavior with a panel of seven microbes, and the copper and palladium complexes were found to be highly active against Gram positive bacteria. The 4 compounds were also tested in human topoisomerase IIα DNA relaxation assays and all three metal complexes had topoisomerase inhibition at a concentration between 4 - 6 micro-molar. The 4 compounds were also tested for activity with the HEK293T cell line and also the breast cell cancer line, MDA-MB-231. The most effective compound for activity against the HEK293T cell line was the [Cu(APZ-tBTSC)Cl] complex, and the MDA-MB-231 breast cancer cell line was the [Pt(APZ-tBTSC)Cl] complex.
Ibrahim Kasujja
Open Journal of Medicinal Chemistry, Volume 11, pp 1-15; https://doi.org/10.4236/ojmc.2021.111001

Abstract:
Melaleuca (tea tree) oil has become increasingly commonly used in recent decades. The essential oil in Australia for the past 120 years is now available globally as an active component in various products. Historically, Melaleuca oil is known for its antiseptic and anti-inflammatory actions. Currently, microwave technology is applied to extract Melaleuca oil, but this extraction technology is not commercially under practice. Traditionally, Melaleuca oil extraction is possible through steam distillation of the Melaleuca alternifolia terminal branches and leaves, and the resultant extract is always either clear or pale yellowish. Melaleuca oil has been promoted as a therapeutic agent because scientific studies indicate that the Rideal-Walker (RW) coefficients of its extract composition include 8 for cymene, 16 for terpineol, 13.5 for tepinen-4-ol and 3.5 for cineole. The mode of action against bacteria is now partially elucidated, and assumptions exist. Hydrocarbons partition into biological membranes to disrupt the vital functions of Melaleuca oil, and also its components behave in the same manner. Therefore, the inhibition of respiration and the leakage of ions or loss of intracellular material and the inability to maintain homeostasis reflect the loss of membrane integrity and lysis in Melaleuca oil products containing lower than usual terpenes concentrations. Melaleuca oil possesses antifungal properties and is known exclusively for the treatment of Candida albicans. This essential oil strongly changes the permeability of Candida albican cells. C. albicans treatment with 0.25% tea tree oil leads to propidium iodide uptake. However, a significant loss of 260-nmlight-absorbing materials after staining with methylene blue occurs after 6 hours. Melaleuca extracts alter the permeability of Candida glabrata that occurs when the membrane is treated with 0.25% Melaleuca oil. Melaleuca oils possess antiviral properties but most findings evidence that this oil fights against both non-enveloped and enveloped viruses, although the range of viruses tested to date is minimal. Melaleuca oil is known for its antiprotozoal activity because it causes a 50% reduction in the growth of protozoa Leishmania major and Trypanosoma brucei at concentrations of 403 mg/ml and 0.5 mg/ml, respectively, based on the studies done (in comparison to controls). An investigation has shown that terpinen-4-ol also contributes significantly to antiprotozoal activity. Tea tree oils at 300 mg/ml killed all cells of Trichomonas vaginalis, and also anecdotal in-vivo studies evidence that Melaleuca oil may be effective in treating infections caused by Trichomonas vaginalis. This review article summarizes the developments in our understanding of the phytochemistry, bioactivity, metabolism and the economic aspects of Melaleuca alternifolia, and it details how Melaleuca alternifolia species have evolved in the ecosystem.
Achi Patrick-Armand, Coulibali Siomenan, Zon Doumade, Timotou Adéyolé, Bolou Eric, Touré Daouda, Sissouma Drissa, Adjou Ané
Open Journal of Medicinal Chemistry, Volume 11, pp 27-39; https://doi.org/10.4236/ojmc.2021.113003

Abstract:
A series of 2-(benzylthio)pyrimidines (6a-l) and 2-(benzimidazolylmethylthio)-pyrimidines derivatives (6m and 6n) analogues of ethyl 2-(benzylthio)-6-methyl-4-phenyl-1,4-dihydropyrimidine-5-carboxylates and ethyl 2-(((1H-benzimidazol-2-yl)methyl)thio)-6-methyl-4-phenyl-1,4-dihydropyri-midine-5-carboxylates were prepared and evaluated for antibacterial activity. These compounds were obtained by condensation of 2-thiopyrimidines (4) with benzyl halides or 2-(chloromethyl)-1H-benzimidazole (5) in the presence of a base. All compounds were characterized by 1H, 13C and HRMS spectra. Out of fourteen, only eight compounds were screened against multi-resistant strains of Escherichia coli and Staphylococcus aureus. The results revealed that all of them were found to possess significant antibacterial activity against the germs tested. Compounds 6c, 6d, 6h and 6m were more active on S. aureus and compounds 6h and 6m more active on E. coli.
Coulibaly Bamoro, Fante Bamba, Koffi Téki Dindet Steve-Evanes, Aurélie Vallin, Vincent Chagnault
Open Journal of Medicinal Chemistry, Volume 11, pp 17-26; https://doi.org/10.4236/ojmc.2021.112002

Abstract:
Due to the continuous emergence and rapid spread of drug-resistant strains of bacteria, there is an urgent need for the development of novel antimicrobials. Along this line, the synthesis and antibacterial activity of 4,5-diphenylimidazol-2-thiol derivatives 2a-g and 6a-e are reported. The structures of the synthesized compounds were confirmed by Nuclear Magnetic Resonance (NMR) and High Resolution Mass Spectrometry (HRMS). All compounds were screened in vitro for their antibacterial activity against Pseudomonas aeruginosa and Escherichia coli (Gram-negative bacteria) and also against Staphyloccocus aureus and Enterococcus faecalis (Gram-positive bacteria). The results showed most of the synthesized compounds have no antibacterial activity. However compound 6d was two-fold potent than ciprofloxacin against Staphylococcus aureus with Minimum Inhibitory Concentration (MIC) of 4 μg/mL and 6c showed moderate biological activity against Staphylococcus aureus (16 μg/mL) and Enterococcus faecalis (16 μg/mL).
Aminata P. Nacoulma, Moussa Compaoré, Naamwin-So-Bawfu Romaric Meda, Laurent Pottier, Véronique Megalizzi, Issa Some, Martin Kiendrebeogo
Open Journal of Medicinal Chemistry, Volume 11, pp 41-57; https://doi.org/10.4236/ojmc.2021.114004

Abstract:
Over the past years, natural products have been used as useful candidates for prevention and treatment of skin disorders such as skin darkening. In this current research, Daniellia oliveri which was a potential source of cosmeceutical agent was selected to investigate its active components. Daniellic acid isolated from the oleoresin was characterized by using data from 1H-NMR, 13C-NMR, HSQC, IR, and online chemo-informatic analysis. The daniellic acid antioxidant, anti-proliferative, and tyrosinase inhibition capabilities were evaluated. This compound possessed an anti-DPPH and iron (III) reducing effect compared to quercetin. It was able to inhibit 9 tumor cells with IC50 going from 0.03 mM (U373) to 0.14 mM (Malme-3M). Interestingly daniellic acid inhibits tyrosinase activity with 1.20 mM as IC50. The tyrosinase inhibition mechanism was noncompetitive mixed-type with un-significant effect on cell melanogenesis. Daniellic acids induced a half-reduction of melanin production in B16F10 cell in IBMX stimulation (p 0.05). The same observation was effective in Malme-3M melanin production with a significant daniellic acid action than kojic acid (p 0.05) without reducing cell viabilities. This bioactive daniellic acid could explain the traditional uses of oleoresins from Daniellia oliveri for genitor-urinary tract diseases treatments, wound healing, and skin ailments in Burkina Faso.
Aisha Abusetta, Jowhara Alumairi, Mariam Y. Alkaabi, Ruba Al Ajeil, Asma Abu Shkaidim, Dana Akram, J. Pajak, Mohammad A. Ghattas, Noor Atatreh, Shaikha S. AlNeyadi
Open Journal of Medicinal Chemistry, Volume 10, pp 15-34; https://doi.org/10.4236/ojmc.2020.101002

Abstract:
Bacterial infections present a serious challenge to healthcare practitioners due to the emergence of resistance to numerous conventional antibacterial drugs. Therefore, new bacterial targets and new antimicrobials are unmet medical needs. Rhodanine derivatives are known to possess potent antimicrobial activities. In this study, we determined the activity spectrum of a series of new rhodanine derivatives against representative Gram-positive and Gram-negative bacterial strains. Compounds 3a and 5a had the highest activity with minimum inhibitory concentrations in the range of 1.12 - 2.5 μg/mL. Transmission electron microscope results confirmed that activities against bacteria occurred via rupturing of the cell wall. Molecular modeling results suggested that rhodanine derivatives have the potential to irreversibly bind to the penicillin-binding protein (PBP) Ser62 residue in the active site. Thus, our results suggested that these rhodanine derivatives could be potential antibacterial drug candidates with strong activity against Gram-negative bacteria.
Ouattara Mahama, Koné Aboudramane, Koné Soleymane, Collet Sylvain, Diomandé Sekou, Sissouma Drissa
Open Journal of Medicinal Chemistry, Volume 10, pp 113-127; https://doi.org/10.4236/ojmc.2020.103006

Abstract:
The present pharmacochemical and modelling work focused on a benzimidazolyl-chalcone series. These previously synthesized compounds were evaluated in vitro for their anticancer activities against a panel of seven human cancer cell lines and normal fibroblasts. Among the new benzimidazole-supported chalcones, nine (9) compounds (compounds 1 - 4, 6 - 8 and compounds 10 and 11) showed promising anticancer activities with IC50s ranging from 0.83 to 2.58 μM. Compounds 2 and 6 with IC50s of 0.83 and 0.86 μM, respectively, were shown to be potent inhibitors of HCT-116 colon cancer cell proliferation. It was therefore necessary, for a development of this new series of chalcones, to establish through a QSAR study, their quantum descriptors according to the DFT calculation method and following the B3LYP/6-31+G (d,p) theory. These descriptive and predictive studies focused on the colon HCT 116 cell line which was found to be more sensitive to the anticancer action of our benzimidazolyl-retrochalcones. QSAR study showed that the electronic energy (Eelec), lipophilicity (logP), chemical softness (S) and chemical hardness (η) of benzimidazolyl-retrochalcones play an important role in inhibiting cancer cell proliferation.
Ouattara Mahama, Coulibaly Songuigama, N’Guessan Deto Jean-Paul
Open Journal of Medicinal Chemistry, Volume 10, pp 57-112; https://doi.org/10.4236/ojmc.2020.103005

Abstract:
Antibiotic macrolides are experiencing renewed interest in anti-infective therapy since the advent of ketolides. This therapeutic class was introduced in order to broaden the narrow antibacterial spectrum of macrolides and to cope with the emergence of germs resistant to Erythromycin A and its hemisynthetic derivatives or neomacrolides (Clarithromycin, Roxithromycin, Azithromycin, Dirithromycin). From a pharmacochemical point of view, ketolides were first of all obtained by operating chemical modulations on Erythromycin A to obtain the neomacrolides, then, by replacing the neutral sugar (L-cladinose) in C3 by a ketone function coupled with the creation of an oxazolidinone like heterocycle in C11 and C12 in place of the hydroxyls present in these positions (Telithromycin, Cethromycin, Solithromycin). These modulations have enabled the improvement of the chemical stability of ketolides in gastric acid medium and increase their affinity for the ribosomal target, hence the broadening of their spectrum of action towards Gram positive germs including strains resistant to other macrolides and to neomacrolides. Therefore, the objective of this systematic review is to report the various pharmacochemical aspects undertaken since 1952 in the macrolide series based on the structure of Erythromycin A. These aspects will focus on the pharmacomodulations that have led, year after year, to the optimization of stability, the improvement of the pharmacodynamic and pharmacokinetic profile and that have allowed the development of neomacrolides, ketolides and neoketolides, which are today essential in the management of severe bronchopulmonary infections.
Verma Deepshikha, Pillai V. N. Rajasekharan
Open Journal of Medicinal Chemistry, Volume 10, pp 46-55; https://doi.org/10.4236/ojmc.2020.102004

Abstract:
With the help of the solid phase peptide synthesizing method, we synthesized Kalata B2 cyclotide and the final product was purified by preparative HPLC. The sequence of Kalata B2 is GLPVCGETCFGGTCNTPGCSCTWPICTRD and its m/z M + H mass is 2955.53. It had been first isolated from Oldenlandia affinis plant leaves extract which belongs to Rubiaceae family. The synthesis of Kalata B2 has been characterized through UPLC/MS, LC/MS, CD, 1HNMR, and IR.
Shaikha S. Al Neyadi, Abdu Adem, Naheed Amir, Ibrahim M. Abdou
Open Journal of Medicinal Chemistry, Volume 10, pp 35-45; https://doi.org/10.4236/ojmc.2020.102003

Abstract:
The peroxisome proliferator activator receptor-γ (PPAR-γ) remained the most effective target for management of diabetes mellitus. The present work endeavors rational designing new PPAR-γ agonist bearing cyclotriphosphazene and thiazolidine-2,4-dione scaffolds. Thiazolidinedione (TZD) derivatives are the novel class of oral antidiabetic drugs which are selective agonist for the nuclear PPARγ that enhances the transcription of several insulin responsive genes but TZDs are known to cause weight gain, hepatotoxicity and fluid retention. So, cyclotriphosphazene containing thiazolidine-2,4-dione was designed, synthesized as PPARγ agonist. The in-vitro antidiabetic activity showed that compound 8 has similar activity and exhibited higher glucose uptake in comparison to pioglitazone as reference drugs. This research opened new avenues for smart designing of molecules with high efficiency towards the management of hyperglycemia.
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