Open Journal of Medicinal Chemistry

Journal Information
ISSN / EISSN : 21643121 / 2164313X
Current Publisher: Scientific Research Publishing, Inc. (10.4236)
Total articles ≅ 67
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Latest articles in this journal

Abdeltawab M. Saeed, Ibrahim M. Abdou, Alaa A. Salem, Mohammad A. Ghattas, Noor Atatreh, Shaikha S. Alneyadi
Open Journal of Medicinal Chemistry, Volume 10, pp 1-14; doi:10.4236/ojmc.2020.101001

Quinoline analogues exhibited diversified biological activities depending on the structure type. A number of natural products with pyrano[3,2-c]quinolone structural motifs and patented chromenes were reported as promising cytotoxic agents. A molecular docking study was employed to investigate the binding and functional properties of 3-amino pyranoquinolinone 2a-c as anti-cancer agents. The three 3-amino pyranoquinolinone 2a-c showed an interesting ability to intercalate the DNA-topoisomerase complex and were able to obtain energetically favorable binding modes (−8.3 - −7.5 kcal/mol). Compound 2c containing butyl chain superiority over the other two compounds 2a-b which appeared to be involved in arene-H interactions with the two dG13 aromatic centers. The butyl chain also appeared to be immersed into a side subpocket formed by the side chains of Asn520 and Glu522 and the backbone amide of Arg503, Gly504, Lys505 and Ile506. Hence, the 3-amino pyranoquinolinone 2c used as starting material to prepare derivatives of pyrano[3,2-c]quinolone containing 1,2,4-triazine ring 4a-b which will enhance the anti-cancer activity. Pyrano[3,2-c]quinoline-2,5-diones 2a-c and 4a-b were evaluated in vitro on cell lines Ehrlich Ascites carcinoma cells (EAC), liver cancer cell line Hep-G2 and breast cancer cell line MCF-7 for the development of novel anticancer agents. The screening results revealed that compounds 4a-b were found most active candidates as anticancer agents.
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; doi:10.4236/ojmc.2020.101002

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, Coulibaly Songuigama, N’Guessan Deto Jean-Paul
Open Journal of Medicinal Chemistry, Volume 10, pp 57-112; doi:10.4236/ojmc.2020.103005

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; doi:10.4236/ojmc.2020.102004

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; doi:10.4236/ojmc.2020.102003

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.
Sameena E. Tanwir, Ajay Kumar
Open Journal of Medicinal Chemistry, Volume 9, pp 1-35; doi:10.4236/ojmc.2019.91001

Alzheimer’s disease (AD) is a neurodegenerative disease distinguished by progressive cognitive deterioration along with declining activities of daily living and behavioral changes. It is the commonest type of pre-senile and senile dementia. Many new therapeutic strategies have been developed in the last few years. We aimed at reviewing the evidence supporting these new therapeutic targets, including anti-amyloid and anti-Tau strategies. This review is focused on important future direction in investigation of potential therapeutic targets for AD drug discovery. Medical advances have improved treatment of many diseases but still there is a need to establish new tools for early diagnosis of AD. A thorough comprehensive understanding of the unexplored mechanism can ameliorate the diagnostic and therapeutic management of AD. There have been several disease-modifying therapeutic strategies for AD in the last few years and are presently at various phases of investigation. Few of them have shown promising results, but their safety and efficacy need to be further explored.
Ryan Beni, William Boadi, Kaleh Karim, Jawzah Alnakhli, Samiyah Alhamed, Beni Ryan, Boadi William, Karim Kaleh, Alnakhli Jawzah, Alhamed Samiyah
Open Journal of Medicinal Chemistry, Volume 9, pp 37-47; doi:10.4236/ojmc.2019.92002

Leuprorelin® (LEP) is an FDA drug for breast cancer and prostate cancer treatment. There are several reported adverse effects such as transient hypertension, excessive salivation, and increased dysuria during treatment with LEP. In this study, the efficacy and toxicity of LEP were modified by using a drug delivery system to adjust the physicochemical properties. In this regard, Leuprorelin® conjugates of triphenylmethanol derivatives (TPMs) were synthesized as prodrugs. Comparative antiproliferative assays showed that LEP-TPMs conjugates had significantly higher antiproliferative activities than the corresponding non-covalent physical mixtures of the TPMs and LEP against human invasive ductal carcinoma (BT-549), human prostate carcinoma (PC3), human lung cancer (A549) and mouse pre-adipocytes (3T3-L1) cells.
Samiyah Alhamed, Jawzah Alnakhli, William Boadi, Ryan Beni
Open Journal of Medicinal Chemistry, Volume 9, pp 49-62; doi:10.4236/ojmc.2019.93003

Antioxidants are substances that can prevent or slow damage to cells caused by free radicals, unstable molecules that the body produces as a reaction to environmental and other pressures. Free radicals may play a role in heart disease, cancer and other diseases. If the body cannot process and remove free radicals efficiently, oxidative stress can result. This can harm cells and body function. Free radicals are also known as reactive oxygen species (ROS). In this research, Triptorelin® (TRP) conjugates of triphenylmethanol derivatives (TPMs) were synthesized to evaluate their in vitro lipid peroxidation potency. Comparative lipid peroxidation assays between TRP-TPMs conjugates and the corresponding TPMs derivatives were measured using thiobarbituric reactive substance (TBARS) in a dose- and time-dependent manner following the Fenton’s pathway. Overall, TBARS decreased between 20% - 30% for the treated samples of synthesized conjugates compared to their respective control physical mixtures. These data suggest that TRP-TPMs derivatives can be used to improve the biological activity of TRP.
B. Ramachandra, N. Venkatasubba Naidu
Open Journal of Medicinal Chemistry, Volume 8, pp 15-21; doi:10.4236/ojmc.2018.82002

Simple, selective and sensitive spectrophotometric method has been developed for the determination of Azacitidine in pharmaceutical formulations and blood with MBTH (3-methyl-2-benzothiazolone hydrazone hydrochloride) reagent, at PH_4.0 which is extractable at 620 nm. Beer’s law is obeying in the concentration ranges 10 - 35 µg∙ml−1 for formulations and 4 - 24 µg∙ml−1 for blood sample. %R.S.D was found to be 0.0240%, 0.0610 and Recovery 99.82% 99.24% respectively. The method was completely validated and proven to be rugged. The interferences of the other ingredients and excipients were not observed. The repeatability and the performance of the proven method were conventional by point and interior proposition and through recovery studies.
Matthew Onyema Agu, Barminas Jeff Tsware, A. Osemeahon Sunday, Jude Chinedu Onwuka, Hotton Joseph Anthony
Open Journal of Medicinal Chemistry, Volume 8, pp 1-14; doi:10.4236/ojmc.2018.81001

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