Shaik Ibrahim Khalivulla

Diabetes is largely developing in the human population due to modern and sedentary lifestyles, leading to serious health complications that affect nerves, eyes, and kidneys. Organophosphorus compounds have diverse pharmacological properties, including antidiabetic properties. In the recent literature, α-aminophosphonates were prepared by green synthesis using orange peel as a biocatalyst. In the current study, we have prepared the same compounds via Pudovik reaction using substituted aromatic aldehydes, aniline, and diethyl phosphite with Cassia fistula fruit pulp (CFFP) as a natural catalyst under reflux. The reaction mechanisms of imine (Schiff’s base) formation and Pudovik reaction products (5a-5h) were presented. Their antidiabetic potential was evaluated through molecular docking and in vitro studies against α-amylase and α-glucosidase. Notably, the compounds 5f, 5e, and 5d showed strong dual inhibitory activity with binding energies of -6.7848, -6.7843 and -6.7598 KCal/Mol, respectively, for 1B2Y and, -9792, -6.8492 and -6.808 KCal/Mol, respectively, for 5NN8 at active site residues; similarly, for in vitro studies the compounds exhibited inhibitory activity against IC50 values 0.75, 2.17, 4.51 µg/ml, respectively, for α-amylase and, 0.38, 1.81, 3.76 µg/ml, respectively, for α-glucosidase enzymes. Among these are also compounds 5f, indicating promising antidiabetic lead compounds, warranting further drug development studies for a therapeutic candidate. This study contributes to the existing literature by introducing CFFP as a novel, natural catalyst for the Pudovik synthesis of α-aminophosphonates and providing comprehensive dual inhibitory antidiabetic data against α-amylase and α-glucosidase.

The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neu- rons causing the cognitive behavioural prob- lems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of De- mentia. Recent data by World Health Organisa- tion indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neu- rofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no perma- nent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, ce- rebrosides, the natural secondary metabolites identified from different taxa with potential neu- roprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from fungi, plant and animal taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebro- sides can increase the cognitive functions by regulating or interacting with the N-methyl-D-as- partate (NMDA) calcium ion (Ca2+) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau pro- teins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB). This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegen- erative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibi- tors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation re- vealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form

A new series of 1,2,3-triazole-tethered xanthone derivatives have been prepared from propargyl­oxyxanthone and various aromatic azides via 1,3-dipolar cycloaddition reaction in the presence of copper(I) iodide as catalyst. The procedure proved to be easy, high yielding, and selective. The synthesized compounds were characterized by using ¹H and ¹³C NMR, mass spectrometry, and elemental analysis and were screened for their antimicrobial activity. Most of these compounds showed moderate to high activity.

The Dementia disease is characterised by neuropsychiatric disturbances due to lack of proper synaptic communication between neurons causing the cognitive behavioural problems. The Alzheimer’s disease (AD) in elderly population is one of the several forms of Dementia. Recent data by World Health Organisation indicates that nearly 10 million people are getting dementia every year, of which 60-70% accounts for AD. The etiology of AD involves the formation of amyloid-β plaques and neurofibrillary Tau tangles in the brain resulting in the death of neural cells. There is no permanent solution for AD treatment, except the FDA approved drugs like galantamine, donepezil, rivastigmine and memantine that are normally associated with side effects. At this juncture, cerebrosides, the natural secondary metabolites identified from different taxa with potential neuroprotective effects offer a promising scope for the treatment of AD. In this paper, cerebrosides reported from all taxa are pooled up along with their functions and listed. The review of literature revealed that Cerebrosides can increase the cognitive functions by regulating or interacting with the N-methyl-d-aspartate (NMDA) calcium ion (Ca²⁺) channels at post-synaptic receptor; nitric oxide (NO); Bcl2, Bax, amyloid precursor (APP) and Tau proteins; brain-derived neurotrophic factor (BDNF) and cAMP- response element-binding proteins (CREB).This indicates that the Cerebrosides could be potential therapeutic agents for the protection of neurons involved in neurodegenerative disease like Alzheimer’s disease. The current neuroprotective drugs are AChE inhibitors; hence, in the present investigation, in silico molecular docking study on cerebrosides for the inhibition of AChE was assessed to find out their capacity to interact with an active catalytic site of AChE. The results of present investigation revealed that all 22 cerebrosides selected for this work interacted with catalytic active site of AChE measured in terms of Gibbs free binding energy. Of all the cerebrosides assessed, compound 6 exhibited strong interaction, followed by 15. This is the first report of molecular docking study on cerebrosides for AChE enzyme inhibition for treatment of Alzheimer’s disease. Nevertheless, detailed in vitro and in vivo, biochemical and molecular investigations are needed to bring them to useful form.

Background: Diabetes is a chronic disease affecting a large population worldwide and stands as one of the major global health challenges to be tackled. According to World Health Organization, about 400 million are having diabetes worldwide and it is the seventh leading cause of deaths in 2016. Plant based natural products had been in use from ancient time as ethnomedicine for the treatment of several diseases including diabetes. As a result of that, there are several reports on plant based natural products displaying antidiabetic activity. In the current review, such antidiabetic potential compounds reported from all plant sources along with their chemical structures are collected, presented and discussed. This kind of reports are essential to pool the available information to one source followed by statistical analysis and screening to check the efficacy of all known compounds in a comparative sense. This kind of analysis can give rise to few numbers of potential compounds from hundreds, whom can further be screened through in vitro and in vivo studies, and human trails leading to the drug development. Methods: Phytochemicals along with their potential antidiabetic property were classified according to their basic chemical skeleton. The chemical structures of all the compounds with antidiabetic activities were elucidated in the present review. In addition to this, the distribution and their other remarkable pharmacological activities of each species is also included. Results: The scrutiny of literature led to identification of 44 plants with antidiabetic compounds (70) and other pharmacological activities. For the sake of information, the distribution of each species in the world is given. Many plant derivatives may exert antidiabetic properties by improving or mimicking the insulin production or action. Different classes of compounds including sulfur compounds (1-4), alkaloids (5-11), phenolic compounds (12-17), tannins (18-23), phenylpropanoids (24-27), xanthanoids (28-31), amino acid (32), stilbenoid (33), benzofuran (34), coumarin (35), flavonoids (36-49) and terpenoids (50-70) were found to be active potential compounds for antidiabetic activity. Of the 70 listed compounds, majorly 17 compounds are from triterpenoids, 13 flavonoids and 7 are from alkaloids. Among all the 44 plant species, maximum number (7) of compounds are reported from Lagerstroemia speciosa followed by Momordica charantia (6) and S. oblonga with 5 compounds. Conclusion: This is the first paper to summarize the established chemical structures of phytochemicals that have been successfully screened for antidiabetic potential and their mechanisms of inhibition. The reported compounds could be considered as potential lead molecules for the treatment of type-2 diabetes. Further, molecular and clinical trials are required to select and establish the therapeutic drug candidates.

Background: Typhonium is the largest genus in the Araceae family (~70 species), distributed in South Asia, Southeast Asia and Australia. Typhonium is well-known for its ethnopharmacological uses, and Southeast Asians consider it as an alternative medicine to treat cancer. This review elucidated the confirmed chemical structures of the isolated compounds of Typhonium and emphasized on their anticancer activities against various human cancer cells. Methods: Among several species, Typhonium blumei, T. flagelliforme, T. divaricatum and T. giganteum were extensively studied due to the presence of a class of secondary metabolites. All the available reports on Typhonium were included and discussed in this article. Results: Until now several groups of compounds, namely amino acids (1, 2), cinnamic acid (3), fatty acids (4-14), glycerol derivatives (15-18) and cerebrosides (19-34), flavonoids (35), hydantoins (36-38), lignin monomers (39-44), nucleobases (45-48), pheophorbides (49-52), phthalate (53), terpene and steroids (54-59) and vitamins (60, 61) were isolated and characterized from Typhonium. These phytochemicals were investigated for their anticancer properties, and results confirmed the promising growth inhibitory effect and anticancer activities against human lung, breast, prostate and colon cancer cells. The anticancer activity of these compounds appears to be mediated through the induction of apoptotic cell death. These phytochemicals further reported to exhibit other pharmacological efficacies, including anti-inflammatory, antioxidant, antiviral, anti-allergic, neuroprotective and hepato-protective properties. Conclusion: This is the first review to summarize the anticancer properties of all isolated compounds of Typhonium genus with confirmed chemical structures. Further advanced studies are necessary to establish the detailed signaling pathways that are involved in the anticancer property of the compounds.

Objective: To investigate the wound-healing effect of Alocasia longiloba (A. longiloba) petiole extract on wounds in rats. Methods: Twenty-two male Sprague-dawley rats were randomly assigned to receive 10% solcoseryl gel, phosphate buffer saline, 50% ethanol, 95% ethanol and hexane extracts of A. longiloba at 1.5%, 3% and 6% doses, respectively. A full thicknesses wound (6 mm) was created on the dorsal of the rat; and all rats were applied with the extract solutions, 10% solcoseryl gel and phosphate buffer saline once a day topically until day 12. The wound was photographed on day 1, 6 and 12, and the percentage of wound contraction was calculated. On day 12, rats were sacrificed and histological examination of granulation tissue was carried out using haematoxylin & eosin and Masson’s Trichrome stain to determine the wound healing effect. Results: In this study, 6% of 50% and 95% ethanol extracts of A. longiloba showed 82.50% and 82.32% wound contraction, respectively, and were comparable with 10% solcoseryl gel (82.30%). Meanwhile, phosphate buffer saline treated group showed the lowest wound contraction (69.86%). Histological assessment of wound treated with 6% of 95% ethanol extract of A. longiloba showed distinct epidermal and dermal layer, higher proliferation of fibroblast and more angiogenesis with collagen compared to other wound treated groups. Conclusions: A. longiloba petiole extracts have a wound healing potential and 6% of 95% ethanol extract of A. longiloba is more effective. Further studies are required to understand the wound healing mechanism of action of the extract.

Background: Clinacanthus nutans Lindau (family: Acanthaceae), also known as “Sabah Snake Grass” or “Belalai Gajah” in Malaysia, has been widely used by Malaysians due to its anticancer property. However, the anticancer activity of C. nutans leaves extract and its safe use need to be further investigated. The objectives of the present study were to evaluate the cytotoxic effects of methanol leaves extract of C. nutans in various human cancer cell lines and to evaluate the in vitro effect of C. nutans leaves on the activity of CYP3A4 and CYP2E1 in human liver microsomes. Methods: The cytotoxic effects of methanol extract of C. nutans leaves in various cancer cell lines (Hep-G2, A549, HT-29, MDA-MB-231, MCF-7, and CRL 1739) and normal cells (3T3) were determined using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cell proliferation assay. The activities of CYP3A4 and CYP2E1 were determined using simple spectrophotometric methods. Results: Results obtained showed that the methanol extract of C. nutans leaves exhibited the highest cytotoxic effect against Hep-G2 cell lines (liver cancer) (IC ₅₀ =13.33 μg/mL), followed by breast cancer oestrogen negative (MDA-MB-231) (IC ₅₀ of 18.67 μg/mL). Methanol leaves extract of C. nutans showed significant inhibition (pC. nutans exhibited the highest cytotoxic activity against liver cancer cells (Hep-G2). There is a possibility that herb-drug interaction could occur with C. nutans through inhibitory effects on CYP3A4. Additionally, inhibition of C. nutans on CYP2E1 could show anti-carcinogenesis effects in human liver microsomes.