Current Drug Discovery Technologies - Volume 18, Issue 6, 2021

Background: Obesity is a common health concern among all populations and age groups worldwide and is a risk factor that leads to a significant increase in mortality and cardiovascular diseases, type 2 diabetes, metabolic syndrome, stroke, and cancer. Disappointing results and weight regain after stopping lifestyle modification or drug therapy indicate the need for other methods of treatment to achieve better and longer effective results. Objective: In this study, the effects of the Apiaceae plants, including Carum carvi L., Bunium persicum Boiss., Cuminum cyminum L., Anethum graveolens L., Foeniculum Vulgare Mill. and Trachyspermum ammi L., in the TPM to treat obesity, were compared to a modern database, covering all in vivo and clinical trials on animal models or humans. Methods: In TPM sources, we used the keywords, “Saman-e- Mufrat”, “Hazāl”, and “Mohazzel”. Each of the six plants was searched in the electronic databases, including Pubmed, Scopus, and Embase from 1975 to 1/1/2020 using keywords, namely “body mass”, “body weight” and “obesity”. Results: The results indicated that six plants had reducing effects on body weight, BMI, fat mass, and appetite in almost all clinical studies on humans and some studies on animals. Conclusion: Since the TPM is a rich source of information about the medicinal properties and effects of medicinal plants, investigating the therapeutic effects of plants from the perspective of TPM can represent the vision of a new horizon in the treatment of many diseases.

Micro-RNAs (miRNA) are short non-coding sequences involved in the biological regulatory process. The miRNAs show a unique expression in diseases, resulting in pathogenesis. Identifying the novel compounds is interesting during this process. The miRNA is a biomarker that helps to detect cancer at an early stage through pathogenesis. Azobenzene and pyrazole are novel compounds, having a cytotoxic effect on cancer cells. These novel compounds are molecular probes used in breast cancer therapy. The viral-based systems have few limitations, such as toxicity and immunogenicity. Therefore, the non-viral based lipoplex and polyplex systems are attractive due to no size limitations for the transfection of micro RNAs. The conventional drug delivery systems have a large size and low drug efficacy at the target site. The nanoparticles prepared by nanoprecipitation methods are attractive in cancer therapy. Thus, the miRNA acts as a powerful tool and identifies the drug target in cancer therapy.

Medicinal plants and dietary supplements may provide an effective and safe treatment for pain relief. Green tea is one of the most common beverages with many several pharmacological activities. The results of various studies have indicated that green tea possesses antinociceptive effects. Many of the protective effects of green tea in terms of pain relief are attributed to its antioxidant and anti-inflammatory properties. Epigallocatechin -3-gallate (EGCG), as one of the major phytochemical components in green tea, is effective in the management of pain through suppression of inflammation and oxidative stress. We have reviewed the effects of green tea on pain and also discussed mechanisms involved in pain relief. This review suggests that green tea can be a safe and often effective treatment for pain.

A novel coronavirus termed nCoV-2019 that caused an epidemic of acute respiratory syndrome in humans was first detected in Wuhan, China, in December 2019. nCoV-2019 resulted in thousands of cases of lethal disease all around the world. Unfortunately, there is no specific treatment yet, so a better understanding of the pathobiology of the disease can be helpful. The renin-angiotensin system and its products have several important physiological actions. On the other hand, this system is involved in the pathogenesis of various diseases. In this context, this review article will briefly discuss insights for understanding the role of the angiotensin-converting enzyme 2 (ACE2) receptor as a potentially attractive target for the nCoV-2019-induced acute respiratory syndrome.

Background: Sexual health plays an important role in women’s health and quality of life. Sexual health management is a prerequisite for physical and psychological health of women. Sexual desire, arousal, and orgasm are three factors of female sexual response. Objectives: This study aimed at the evaluation of the studies focusing on herbal medicine on women's sexual function and the assessment of its effectiveness. Methods: So far, many different methods have been known for the treatment of female sexual dysfunction, however, none of them are not efficacious therapy. Results: Generally, the use of herbal medicine is a safe and effective therapeutic method in the treatment of women with sexual dysfunction. Conclusion: The role of herbal and nutritional supplementation in female sexual function has attracted researchers’ interest in recent years.

Aims and Objectives: The biological dataset was retrieved from two series of α-glucosidase inhibitors synthesized by Rahim et al. and Taha et al. and consisted of a total of 46 (forty-six) α- glucosidase inhibitors. Methods: The α-glucosidase inhibitory IC50 values (μM; performed against α-glucosidase from Saccharomyces cerevisiae) were converted into negative logarithmic units (pIC50). The CoMFA and CoMSIA models were developed using 37 as a training set, and externally validated using 9 as a test set. The CoMFA models MMFF94 were generated, ranging from 3.4661 to 5.2749 using leave-oneout PLS analysis cross-validated correlation coefficient q² 0.787, a high non-cross-validated correlation coefficient r² 0.819, with a low Standard Error Estimation (SEE) 0.041, F value 1316.074 and r²pred 0.996. Results: The steric and electrostatic fields contributions were 0.507 and 0.493, respectively. The CoMSIA model q² 0.805, r² 0.833 was attained, (SEE) 0.065, F value 520.302 and r²pred 0.990. Contribution of steric, electrostatic, hydrophobic, donor and acceptor fields was 0.151, 0.268, 0.223, 0.234, 0.124, respectively. Conclusion: The HQSAR model of the training set exhibits a significant cross-validated correlation coefficient q² 0.800 and non-cross-validated correlation coefficient r² 0.943.

Objectives: The present study was conducted to evaluate the antimicrobial effects of the recombinant chimer present in the lactoferrampin-lactoferricin [LFA-LFC] derived from the camel milk on some oral bacteria responsible for dental caries and endodontic failures. Methods and Material: The antimicrobial activity was assessed on the Streptococcus mutans [ATCC 35668], Streptococcus salivarius [ATCC 9222], Streptococcus oralis [ATCC 35037], and Enterococcus faecalis [ATCC 29212], using the microbroth dilution method. The cytotoxicity analysis was done through the MTT method on the human gingival fibroblasts. The data were reported using the descriptive methods and were analyzed by the one-way analysis of variance (ANOVA) and Tukey HSD test. Results: Results showed that the chimeric peptide had the highest bacteriostatic effect on S. salivarius with the lowest minimum inhibitory concentration value of 1.22 μg/Ml. Also, LFA-LFC chimer was more effective against S. mutans and S. salivarius compared to using 0.2% chlorhexidine mouthwash. The minimum bactericidal concentration analysis showed the most bactericidal effect against S. mutans [1.256 μg/mL]. In spite of the greater antibacterial effect on the evaluated streptococci, this peptide showed lower bacteriostatic and bactericidal properties against E. faecalis compared to the chlorhexidine. Based on cytotoxicity assay, over 50% of the cells were viable in all the evaluation times, demonstrating the biocompatibility of the peptide. Conclusion: The LFA-LFC chimer revealed comparable or even more effective antibacterial properties compared to the chlorhexidine mouthwash against the caries-inducing bacteria with no toxicity on the human gingival fibroblast cells. So, this peptide can be used as a safe alternative to chlorhexidine and other chemicals in dental applications for the prevention and management of dental caries.

Background: The anticancer properties of natural products calactin, calotropin and calotoxin are well established. However, the mechanisms of their action are unclear and the molecular targets pertinent to them are not detailed. In this study, potential anti-cancer targets of these compounds have been identified using reverse screening approaches that may provide valuable insights into anticancer drug development. Objective: The aim of the study was to identify the potential anticancer targets of calactin, calotropin and calotoxin using reverse screening strategy. Methods: The ligands were screened for potential targets based on their shape similarity and pharmacophore model matching. The overlapping targets obtained from both methods were verified using the reverse docking approach and validated by docking analysis. MM/PBSA calculation was performed to predict binding affinities between ligand and confirmed targets. Results: Interleukin-2 inducible T cell kinase [ITK] was confirmed as a potential target of calactin (Ki= -10.3 kcal/mol), calotropin (Ki= -8.7 kcal/mol) and calotoxin (Ki= -10.2 kcal/mol). The ligands interacted with hinge region residues such as Met438 and Asp500 which occupy the highly conserved ATP binding site. Binding energies of calactin (ΔEbind = -29.18 kJ/mol), calotropin (-28.57 kJ/mol) and calotoxin (-21.21 kJ/mol) with ITK were higher than (more negative) positive control sunitinib (-15.03 kJ/mol) and standard staurosporine (-21.09 kJ/mol). Besides this, Interstitial collagenase [MMP1] was confirmed as a potential target of calotoxin (Ki= -8.2 kcal/mol). However the binding energy (ΔEbind = -11.89 kJ/mol) was lower compared to positive control batimastat (-21.07 kJ/mol). Conclusion: The results of this study confirmed ITK as a potential target for calactin, calotropin and calotoxin. These compounds can therefore be used as lead molecules for the development of novel ITK inhibitors, which may have immense therapeutic applications as immune-suppressants and as anticancer drugs.

Background & Objective: A facile and efficient method for the synthesis of novel derivatives of FQ citrate conjugates with 1,2,4-triazoles and 1,3,4-oxadiazole scaffolds 8-11 using conventional, as well as microwave irradiation methods, was reported. Based on these original building blocks, the new derivatives of 3, 7-disubstituted fluoroquinolones bearing the oxadiazolyl-triazole groups were obtained. These invaluable derivatives are of great interest in medicinal and pharmaceutical studies because of their important biological properties. Methods: All the reactions were examined under conventional as well as microwave mediated conditions. The structures of obtained compounds were confirmed by ¹H NMR, ¹³C NMR, IR HRMS spectroscopy, and elemental analysis. The antibacterial and antifungal activities of these compounds were screened against Gram-positive, Gram-negative bacteria, and fungal stains by the agar well diffusion method. Cytotoxic assay of the title compounds was evaluated against cervical carcinoma cell line (HeLa) by using the MTT assay. The crystal structure of the Quinolone-DNA cleavage complex of type IV topoisomerase from S. pneumoniae (PDB ID: 3RAE) complex was obtained from the Protein Database (PDB, http:// www.rcsb.org). Molecular properties prediction-drug likeness was studied by Molinspiration and Molsoft software, while lipophilicity and solubility parameters were studied using the Osiris program. Results: A novel approach for the synthesis of benzylthio-1,2,4-triazole and 1,3,4-oxadiazoles core with regioisomeric norfloxacin citrate conjugates was developed. Among the title compounds, 11b, 10a reveal pronounced activity against S. pneumoniae with minimum inhibitory concentrations of 0.89, 0.96 mg/mL and MBCs of 2.95, 2.80 mg/mL, respectively. Minimum Fungicidal Concentration (MFC) has been determined for each compound against two fungal strains. Compound 11b showed maximum anti-cancer activity against HeLa cell line with IC50 value 11.3 ± 0.41 comparable to standard drug DXN. For binding mode, active site residues and docking energies (ΔG =-7.9 Kcal/mol) for ligand 9b exhibited the highest hydrogen bonding (3.59274 A˚), Pi– Alkyl (5.14468 A˚) interactions with amino acid LEU479 of 3RAE protein. The compounds following the Lipinski ‘Rule of five’ were synthesized for antimicrobial and anti-cancer screening as oral bioavailable drugs/leads. Maximum drug likeness model score 1.52, 1.41 was found for compounds 10d, 11b. Conclusion: The present work, through simple synthetic approaches, led to the development of novel hybrids of fluoroquinolone containing citrate-triazole-oxadiazole pharmacophores that exhibited remarkable biological activities against different microorganisms and cell lines. The compounds showed suitable druglike properties and are expected to present good bioavailability profile. An efficient combination of molecular modeling and biological activity provided an insight into QSAR guidelines that could aid in further development and optimization of the norfloxacin derivatives.

Background: Anti-apoptotic protein BCL-XL plays a vital role in tumorigenesis and cancer chemotherapy resistance, resulting in a good target for cancer treatment. Understanding the function of BCL-XL has driven the progression of a new class of cancer drugs that can mimic its natural inhibitors, BH3-only proteins, to trigger apoptosis. This mimicking is initiated through acetogenins due to their excellent biological properties. Acetogenins, which can be isolated from Annonaceae plants, have a unique structure along with several oxygenated functionalities. Objective: Based on their biological capability, various acetogenins were studied in the present study and compared alongside ABT-737 on molecular docking. Methods: The docking simulation of acetogenins was performed using AutoDock Vina software. Results: Our findings have shown eleven acetogenins-BCL-XL protein complex, namely, muricin B (2), muricin F (4), muricin H (6), muricin I (7), xylomaticin (9), annomontacin (12), annonacin (14), squamocin (15), squamostatin A (16), bullatacin (20) and annoreticulin (21) exhibited strong binding affinities lower than – 10.4 kcalmol-1 as compared to ABT-373-BCL-XL complex. Six hydrogen bonds along with hydrophobic interaction were detected on the complex of BCL-XL with muricin B (2), muricin G (5), corossolone (11), and isoannonacin-10-one A (18). Conclusion: These findings indicated that some acetogenins could represent a new potential BCLXL inhibitor that could mimic the BH3-only protein for the induction of apoptosis in cancer chemotherapy.