Open Access Original Research Article

Quantitative Structure–Activity Relationship and Molecular Docking Studies of Imidazolopyrimidine Amides as Potent Dipeptidyl Peptidase-4 (DPP4) Inhibitors

Leila Emami, Razieh Sabet, Amirhossein Sakhteman, Mehdi Khoshnevis Zade

Journal of Pharmaceutical Research International, Page 1-15
DOI: 10.9734/jpri/2019/v27i630186

Type 2 diabetes (T2DM) is a metabolic disorder disease and DPP-4 inhibitors are a class of oral hypoglycemic that blocks the dipeptidyl peptidase-4 (DPP-4) enzyme.  DPP-4 inhibitors reduce glucagon and blood glucose levels and don’t have side effects such as hypoglycemia or weight gain. In this paper, a series of imidazolopyrimidine amides analogues as DPP4 inhibitors were selected for quantitative structure-activity relationship (QSAR) analysis and docking studies. A collection of chemometric methods such as multiple linear regression (MLR), factor analysis-based multiple linear regression (FA-MLR), principal component regression (PCR), genetic algorithm for variable selection-MLR (GA-MLR) and partial least squared combined with genetic algorithm for variable selection (GA-PLS), were conducted to make relations between structural features and DPP4 inhibitory of a variety of imidazolopyrimidine amides derivatives. GA-PLS represented superior results with high statistical quality (R2 = 0.94 and Q2 = 0.80) for predicting the activity of the compounds. Docking studies of these compounds reveals and confirms that compounds 15, 18, 25, 26, and 28 are introduced as good candidates for DPP-4 inhibitors were introduced as a good candidate for DPP-4 inhibitory compounds.

Open Access Original Research Article

Effects of Thioxanthene Containing Anti-Psychotic and Anti-Platelet Drug Combination on Mean Platelet Volume and Platelet Distribution Width in Rats

Muhammad Irfan Bashir, Uzma Saleem, Fareeha Anwer, Bashir Ahmad

Journal of Pharmaceutical Research International, Page 1-7
DOI: 10.9734/jpri/2019/v27i630187

Aim: To evaluate the combined and individual effects of thioxanthene containing antipsychotic and anti-platlet drug on Mean Platelet Volume (MPV) and Platelet Distribution Width (PDW) in rats.

Methods: This investigational study comprised of 100 albino rats of both sexual orientation, they were of 300 g to 350 g. We got ten groups, in which each group consisted of 10 rats (n=10).Ozagrel was used as anti-platelet and Zuclopenthixol was used as thioxanthene containing antipsychotic. Rats were treated with defined doses of Ozagrel and thioxanthene containing anti-psychotic (Zuclopenthixol) alone and in joined for three weeks (21 days). Blood test at 0, seventh, fourteenth and last day of study were taken. Mean Platelet Volume and Platelet Distribution Width were estimated from blood tests by using standard research center procedure. Results were accumulated and abridged by applying statistics. Correlation was framed between all days incentive to zero day values.

Results: Anti-psychotic drug and antiplatelet drug both showed decrease in MPV with both doses highly significantly (p < 0.001) decrease associated with maximum doses alone and with combination group. In case of PDW all individual and minimum combination group showed increase in PDW values but significantly (p < 0.001) increase in maximum combination groups.

Conclusion: Combination of both drugs can cause more decrease in MPV as compare to the individual and in case of PDW combination with maximum doses may cause decrease in values by opposing the results individual therapy. It indicated any Drug-Drug interaction between these two drugs regarding Mean platelet volume and Platelet distribution width.

Open Access Original Research Article

Enhancement of Doxorubicin Cytotoxicity by Verapamil in Human Breast Cancer Cells

Sameer E. Al-harthy, Mashael S. Al-Motairi, Huda M. Al-Kreathy, Fatemah O. Kamel, Mohamed M. Sayed-Ahmed, Etimad Abbas Huwait, Hamdan S. Al-Malkey, Abdel-Moneim M. Osman

Journal of Pharmaceutical Research International, Page 1-10
DOI: 10.9734/jpri/2019/v27i630188

Background: Worldwide, breast cancer is a main cause of morbidity and mortality in females. Doxorubicin (DOX) is an anthracycline anticancer drug and most commonly employed in polychemotherapy protocols in the treatment of solid and hematological tumors. Unfortunately, its optimal clinical benefit is limited secondary to the rapid development of DOX resistance and therapeutic failure.

Aim: Therefore, the current study has been initiated to investigate the possible mechanisms whereby the calcium channel blocker Verapamil (VER) could decrease DOX resistance and enhance the cytotoxic activity of DOX against the growth of human breast cancer cells.

Methodology: To achieve the ultimate goal of this study, we have examined DOX-induced cytotoxicity, apoptosis, alteration in the function of multidrug resistance proteins and cell cycle phase distribution against MCF-7 cell line in presence and absence of Verapamil. 

Results: Addition of VER enhanced the cytotoxic effect of DOX against the growth of MCF-7 cells which manifested as a significant decrease in the IC50 from 36 µg/ml for DOX alone to 13 µg/ml for DOX plus VER.  Moreover, combined treatment with VER and DOX significantly increased percentage of early apoptosis and cells arrested in G0/G1 phase when compared to DOX alone. In addition, VER significantly increased DOX cellular uptake through inhibition of the function of multidrug resistant proteins.  

Conclusion: VER treatment enhanced the cytotoxic activity of DOX against the growth of MCF-7 cells secondary to increase its cellular accumulation.  The observed increase in DOX uptake by VER was parallel to increased accumulation of Rho-123 dye which my point to the contribution of inhibition of multidrug resistant proteins by VER in the enhancement of DOX cytotoxicity.

Open Access Original Research Article

Efficacy of the Peganum Harmala Oil Versus 1% Permethrin Shampoo on the Treatment of Head Louse Infestation

Mina Maarefvand, Hoorieh Mohammadi Kenari, Ali Ghobadi, Alireza Soleimani, Fataneh Hashem-Dabaghian Hashem-Dabaghian

Journal of Pharmaceutical Research International, Page 1-9
DOI: 10.9734/jpri/2019/v27i630190

Introduction: Head louse infestation is one of the major public health problems among children worldwide. Several drugs have been developed to treat the infestation. Side effects and drug resistance associated with these drugs limit their applicability. Increasing attention of scientific committees to alternative drugs along with greater effects and lower complications and costs, increase the hope of success for alternative drugs.

Materials and Methods: 93 participants (11 men and 82 women) with positively diagnosed with head lice infestation were allocated into two groups using the stratified randomization method. The intervention in one group comprised of Peganum harmala oil applied onto the patient’s hair and scalp and the hair and scalp being washed after 20 minutes once a day. The procedure was performed on the first three days of week one of intervention (phase 1) and reiterated on the subsequent week (phase 2) in a similar manner. The other group applied permethrin shampoo once in the first week of intervention and once in the second week.

Results: Permethrin shampoo recovered 7 (29.2%) in day 1, 2 (15.4%) in day 2, 2 (25.0%) in day 3 and 28 (73.7%) in day 11 but Peganum harmala oil recovered 17 (70.8%) in day 1, 11 (84.6%) in day 2, 6 (75.0%) in day 3 and 10 (26.3%) in day 11 (P-value <0.005).  

Conclusion: The clearing effects and side effects of Peganum harmala oil and permethrin shampoo are approximately similar in the two-phase application although the oil’s clearing and protective effect is greater than that of the shampoo with its effect occurring earlier than that of the shampoo.

Open Access Review Article

An Overview of Different Synthetic Routes for the Synthesis of Phthalazine Derivatives

Smita Singh, Nitin Kumar

Journal of Pharmaceutical Research International, Page 1-15
DOI: 10.9734/jpri/2019/v27i630189

This review paper describes the different synthetic routes used for the synthesis of substituted phthalazine derivatives. Phthalazines have been used as building blocks for the synthesis of a new molecule with heterocyclic structure. These new molecules are highly useful in medicinal chemistry for the researchers leading to the further development of new molecules which have potency and effectiveness to produce a desired pharmacological response.