Synthesis and Antinociceptive Activity of Newly Modified Amine Analogs of Phencyclidine in Mice Seyed Ali Sobhanian, Maryam Shokrollahi, Marjaneh Samadizadeh, Mohsen Khalili, Abbas Ahmadi Combinatorial Chemistry and High Throughput Screening, 2022 Background: Phencyclidine (PCP, I) and its substituted analogs are significant and broadly abused psychotomimetic drugs that affect the central nervous system. They possess many pharmacological properties due to the presence of specific receptors in the brain. Aim and Objective: Methyl group, despite strong electron-donating and characters of dipole moments, was placed on various positions of phenyl and amine moieties of phencyclidine along with the substitution of benzylamine, piperazine, and aniline derivatives in place of piperidine ring of phencyclidine to create novel compounds of the core with analgesic properties. Material and methods: For evaluation of the analgesic activities of newly synthesized compounds, they were screened by tests of tail immersion (thermal) and formalin (chemical) pains. The obtained data with the control and PCP groups were also compared. Results: The outcomes indicated that some new compounds have more antinociceptive effects than PCP in tail immersion and formalin tests. In the tail immersion test, the methyl piperazine analog (III) shows more efficacy than others. In the formalin test, none of the compounds are as effective as phencyclidine at the earliest time-point, but compounds IV and V show effectiveness during the second stage of formalin pain. Conclusion: It can be concluded that the methyl-piperazine analog of phencyclidine was the best candidate to decrease acute thermal pain, and benzylamine derivatives were suitable candidates to reduce chemical pains.
Antihyperglycemic and Antihyperlipidemic Evaluation of Zingiber officinale, Anethum graveolens and Citrullus colocynthis Extracts with Different Polarities in Streptozotocin-Induced Diabetic Rats Abbas Ahmadi, Mehrdad Roghani, Meysam Parsianfard, Faeze-sadat Seyedmomeni, Sahar Gheraati, et al. Pharmaceutical Chemistry Journal, 2022 Zingiber officinale (ginger , II ), Citrullus colocynthis (CC, III ) and Anethum graveolens (dill, IV ) are functional medicinal plants containing beneficial compounds and some evidence exists on their anti-diabetic, anti-inflammatory and hypolipidemic activities. The objective of this study was to evaluate the antihyperglycemic and antihyperlipidemic potential of various extracts of these plants with different polarities in experiments on streptozotocin-induced diabetic rats. Test animals ( n = 112) were randomly divided into control, diabetic, diabetic+chloroform extract, diabetic+carbon tetrachloride extract, diabetic+hydroalcoholic extract, and diabetic+aqueous extract groups. Rats were made diabetic by a single injection of streptozotocin (STZ, 60 mg/kg). The plant extracts were daily administered (100 mg/kg, i.p.) for 3 weeks. Serum glucose and lipid levels were measured at different weeks. All extracts of ginger and dill as well as carbon tetrachloride and hydroalcoholic extracts of CC significantly reduced serum glucose level in diabetic groups. In addition, some plants extracts approppriately and significantly improved serum lipid levels including triglyceride, total cholesterol, HDLcholesterol, and LDL cholesterol in diabetic rats. According to extract polarities and components, all ginger extracts exerted hypoglycemic effect, however, hydroalcoholic extract showed the best potential to appropriately modify serum lipids in diabetic condition. In addition, hydroalcoholic extracts of C. colocynthis and A. graveolens had the best anti-diabetic potential which could be related to better extraction of bioactive components by polar or non-polar organic and aqueous solvents from these medicinal herbs.
The Effects of Solvent Polarity on Analgesic and Anti-Inflammatory Activities of Securigera Securidaca (L.), Achillea Eriophora DC, and Portulaca Oleracea Extracts Abbas Ahmadi, Mohsen Khalili, Maryam Salimi, Niloofar Mirsistani, Ayda Niksirat, et al. Pharmaceutical Chemistry Journal, 2019 The effect of solvent polarity on bioactive extraction contents of three famous medicinal plants (Securigera securidaca, Portulaca oleracea and Achillea eriophora) with reported analgesic and anti-inflammatory activities was evaluated by GC-MS analysis. Pain and inflammation-lowering properties of all extracts were evaluated and compared to ibuprofen as well-known nonsteroidal anti-inflammatory drug (NSAID). The results indicated that, more extracted sterols, fatty acids, polyols (or alcohols), phenols, and flavonoids from S. securidaca and P. oleracea as well as antraquinone and terpenes from A. eriophora may be responsible for higher analgesic and anti-inflammatory activities of these herbal extracts. Carbon tetrachloride and chloroform (or dichloromethane) more effectively extract phytochemicals than do aqueous ethanol solutions, which can be related to higher solubility of these compounds in the former non-aqueous organic solvents.
Substituted aminobenzothiazole derivatives of tacrine: Synthesis and study on learning and memory impairment in scopolamine-induced model of amnesia in rat Abbas Ahmadi, Mehrdad Roghani, Sanaz Noori, Babak Nahri-Niknafs Mini Reviews in Medicinal Chemistry, 2019 Background: Currently, there is no conclusive cure for Alzheimer’s disease (AD) and existing treatments mainly offer symptomatic relief. Dysfunction of the cholinergic system plays an important role in the pathogenesis of AD. Tacrine (1, 2, 3, 4-tetrahydroacridin-9-amine, III) was the first approved agent for the palliative therapy of AD but its use is associated with some complications. Development of novel multi target derivatives of Tacrine with lower complications is strongly warranted. In this study, new aminobenzothiazole (1-5, with many useful biological and pharmacological properties) analogues (IV-VIII) were synthesized by changing of amine moiety of III. Then, the effects of these new compounds on learning and memory impairment in scopolamine-induced model of amnesia were studied and the outcomes were compared with control and Tacrine groups in rat. Material and Methods: The rats received Tacrine or its derivatives (IV-VIII) i.p. for two weeks at a dose of 10 mg/kg. For induction of amnesia, scopolamine at a dose of 1 mg/kg was daily administered i.p. started on day-8 till the end of the study. Behavioral experiments including Y-maze, novel object recognition (discrimination) and passive avoidance paradigms were conducted at week 2. Results: Data analysis showed that some Tacrine derivatives, especially VII with 2-amino, 6-nitrobenzothiazole moiety, could markedly and significantly improve alternation score, discrimination ratio and step through latency compared to control and Tacrine groups. Conclusion: These findings indicated that some of these derivatives (especially compounds VI and VII) are capable to mitigate learning and memory deficits in scopolamine-induced model of amnesia in rats and may have potential benefit in management of patients with AD.
New amine and aromatic substituted analogues of phencyclidine: Synthesis and determination of acute and chronic pain activities Maryam Shokrollahi, Marjaneh Samadizadeh, Mohsen Khalili, Seyed A. Sobhanian, Abbas Ahmadi Combinatorial Chemistry and High Throughput Screening, 2019 Background: Phencyclidine (PCP, I) is a synthetic drug with remarkable physiological properties. PCP and its analogues exert many pharmacological activities and interact with some neurotransmitter systems in the central nervous system like particular affinity for PCP sites in NMDA receptors or dopamine uptake blocking or even both. Aim and Objective: The following research, methyl group with electron-donating and dipole moment characters was added in different positions of phenyl ring along with the substitution of benzylamine (with many pharmacological effects) instead of piperidine ring of I to produce new compounds (II-V) of this family with more analgesic activities. Materials and Methods: Analgesic activities of these new compounds were measured by tail immersion and formalin tests for acute and chronic pains, respectively. Also, the outcomes were compared with control and PCP (10 mg/kg) groups. Results: The results indicate that compounds III, IV, and V have more acute and chronic antinociceptive effects than PCP and compound II which may be concerned with more antagonizing activities of these new painkillers for the blockage of dopamine reuptake as well as high affinity for NMDA receptors PCP binding site. Conclusion: It can be concluded that the benzylamine derivative of phencyclidine with a methyl group on the benzyl position on phenyl ring (V) is a more appropriate candidate to reduce acute and chronic (thermal and chemical) pains compared to other substituted phenyl analogs (II-IV) and PCP.
Synthesis and Antinociception Activities of New Substituted Aminobenzothiazole Analogs of Lidocaine Abbas Ahmadi, Mohsen Khalili, Javad Hasanabadi, Mahnaz Rezavil, Babak Nahri-Niknafs Pharmaceutical Chemistry Journal, 2017 Local anesthetics are the most widely used drugs in practical medicine which provide the loss of sensation in a specific body part without loss of consciousness or impairment of central control of vital functions. Lidocaine (I) is the most common local anesthetic drug which has been widely used in all cases because of its excellent diffusing and penetrating properties as well as rapid onset of surgical analgesia. In this study, new aminobenzothiazole analogs (with many useful biological and pharmacological properties) were synthesized by changing the amine moiety of I. The acute and chronic pain properties of new compounds (II – VI) were studied using the tail immersion and formalin tests on mice and the results were compared to control and lidocaine groups. According to the obtained results, aminobenzothiazole derivatives are better candidates than diethylamine group for replacement in the amine moiety of I. In addition, derivatives with electron-withdrawing groups on this amine (V and VI) could decrease pain better than compounds (II and III) with electron-donating groups (especially in position 6 of this amine, II and V) which may be concern to more blockades of specific sodium channels by these compounds.
Synthesis and Antinociception Activities of Some Novel Derivatives of Phencyclidine with Substituted Aminobenzothiazoles Mini Reviews in Medicinal Chemistry, 2017
