Manas Mathur

Evaluation of antidiabetic and antioxidant activity of Moringa oleifera in experimental diabetes

Background:  Moringa oleifera, a widely cultivated species in India, is an exceptionally nutritious vegetable with a variety of potential uses in treating rheumatism, venomous bites, and microbial infections. In the present study, we investigated the antidiabetic and antioxidant effects of methanol extracts of M. oleifera pods (MOMtE) in streptozotocin (STZ)‐induced diabetic albino rats.

Studies on trigonelline from Moringa oleifera and its in vitro regulation by feeding precursor in cell cultures

Trigonelline (N-methylnicotinate) biosynthesized from nicotinate is one of the metabolically active pyridine alkaloid, widely distributed in plant kingdom. In the present study trigonelline has been isolated from various plant parts and callus cultures of Moringa oleifera Lam., Moringaceae, and was identified using TLC, GLC, GC-MS, which was comparable to that of the standard trigonelline. The trigonelline recovery was found to be maximum in the pods and minimum in flowers. In order to enhance the production of trigonelline in vitro grown cultures, different treatment doses of nicotinic acid (250, 500 and 750 mg L-1) were supplemented in the medium as precursor. Maximum increase (up to 1.10 fold) was observed in the treatment dose of 500 mg L-1 of nicotinic acid.

Synthesis, antimicrobial activity, structure-activity relationship and cytotoxic studies of a new series of functionalized (Z)-3-(2-oxo-2-substituted ethylidene)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-ones

A new series of functionalized (Z)-3-(2-oxo-2-substituted ethylidene)-3,4-dihydro-2H-benzo[b][1,4]oxazin-2-ones 23-26, incorporating pharmaceutically privileged substructures such as cyclopropyl, naphthyl, biphenyl and cyclohexylphenyl were synthesized in excellent yields. All the synthesized compounds were screened for their in vitro antibacterial activity against gram-(+)ve and gram-(-)ve bacterial species i.e. S. griseus, S. aureus, B. subtillis and E. coli as well as in vitro antifungal activity against fungal species i.e. F. oxysporium, A. niger, P. funiculosum and T. reesei, respectively. In this study, compounds containing cyclopropyl and cyclohexylphenyl substructures were identified as promising antimicrobial agents than standard drugs, ampicillin and chloramphenicol as well as ketoconazole. SAR study illustrates that electron-withdrawing groups increases the antibacterial as well as antifungal activity of 2-oxo-benzo[1,4]oxazines and vice versa. Compounds 23e and 26e, the most active compounds of the series, displayed promising antibacterial activity than Ampicillin and Chloramphenicol. Moreover, compound 26d showed promising antifungal potency as compared to Ketoconazole. Cytotoxic studies of the active compounds i.e. 23c-e, 24e, 25d and 26d-e found to be non-toxic in nature in 3T3 fibroblast cell lines using MTT assay.

Antiradical efficiency of 20 selected medicinal plants

The antioxidant system of a plant comprises a group of chemicals that are highly diverse in their sources, effects and uses. These antioxidants are capable of contracting and damaging free radicals. This investigation deals with a screening and comparison of the antioxidant activities of 20 selected medicinal plants and their parts, individually and in combination with vitamins A, C or E, using the DPPH radical scavenging method. Phyllanthus emblica L., Santalum album L., Syzygium cumini L. and Trigonella foenum-graecum L. presented highly significant antiradical efficiency (AE) singly and in combination with either vitamin A, C or E. Further, Curcuma longa L., Momordica charantia L., S. cumini, T. foenum-graecum, Moringa oleifera Lam and S. album have also shown fairly significant AE in a vitamin combination dose of 0.001 mM concentration.

Non-peptide-based new class of platelet aggregation inhibitors: Design, synthesis, bioevaluation, SAR, and in silico studies

A series of 2‐oxo‐2‐phenylethylidene linked 2‐oxo‐benzo[1,4]oxazine analogues 17a–x and 18a–o, incorporated with a variety of electron‐withdrawing as well as electron‐donating groups at ring A and ring C, were synthesized under greener conditions in excellent yields (up to 98%). These analogues 17a–x and 18a–o were evaluated for their arachidonic acid (AA)‐induced platelet aggregation inhibitory activities in comparison with the standard reference aspirin (IC50 = 21.34 ± 1.09 µg/mL). Among all the screened compounds, eight analogues, 17i, 17x, 18f, 18g, 18h, 18i, 18l, and 18o, were identified as promising platelet aggregation inhibitors as compared to aspirin. In addition, cytotoxic studies in 3T3 fibroblast cell lines by MTT assay of the promising compounds (17i, 17x, 18f–18i, 18l, and 18o) were also performed and the compounds were found to be non‐toxic in nature. Furthermore, the results on the AA‐induced platelet aggregation inhibitory activities of these compounds (17i, 17x, 18f–18i, 18l, and 18o) were validated via in silico molecular docking simulation studies. To the best of our knowledge, this is the first report of the identification of non‐peptide‐based functionalized 2‐oxo‐benzo[1,4]oxazines as platelet aggregation inhibitors.

Discovery of C-3 Tethered 2-oxo-benzo[1,4]oxazines as Potent Antioxidants: Bio-Inspired Based Design, Synthesis, Biological Evaluation, Cytotoxic, and in Silico Molecular Docking Studies

The discovery of C-3 tethered 2-oxo-benzo[1,4]oxazines as potent antioxidants is disclosed. All the analogs 20a-20ab have been synthesized via “on water” ultrasound-assisted irradiation conditions in excellent yields (upto 98%). All the compounds have been evaluated for their in vitro antioxidant activities using DPPH free radical scavenging assay as well as FRAP assay. The result showed promising antioxidant activities having IC50 values in the range of 4.74 ± 0.08 to 92.20 ± 1.54 μg/mL taking ascorbic acid (IC50 = 4.57 μg/mL) as standard reference. In this study, compounds 20b and 20t, the most active compound of the series, showed IC50 values of 6.89 ± 0.07 μg/mL and 4.74 ± 0.08 μg/mL, respectively in comparison with ascorbic acid. In addition, the detailed SAR study shows that electron-withdrawing group increases antioxidant activity and vice versa. Furthermore, in the FRAP assay, eight compounds (20c, 20j, 20m, 20n, 20r, 20u, 20z, and 20aa) were found more potent than standard reference BHT (C0.5FRAP = 546.0 ± 13.6 μM). The preliminary cytotoxic study reveals the non-toxic nature of active compounds 20b and 20t in non-cancerous 3T3 fibroblast cell lines in MTT assay up to 250 μg/mL concentration. The results were validated via carrying out in silico molecular docking studies of promising compounds 20a, 20b, and 20t in comparison with standard reference. To the best of our knowledge, this is the first detailed study of C-3 tethered 2-oxo-benzo[1,4]oxazines as potential antioxidant agents.

Synthesis and antimalarial activity of novel bicyclic and tricyclic aza-peroxides

For the first time, novel bicyclic 5a–h as well as tricyclic 9a–h aza-peroxides were synthesized using a 1O2-mediated photo-oxygenation methodology as a key step in 52–71% yields in which one of the oxygen atoms of the 1,2,4-trioxane ring has been replaced by a nitrogen atom. The methodology is simple and is an efficient way to access 1,2-dioxa-4-aza six membered ring compounds. All these compounds were assessed for their in vitro antimalarial activity against Plasmodium falciparum. Compound 9a, 9c and 9f, the most active compound of the series, showed IC50 values of 9.43, 8.83 and 5.63 ng mL−1, respectively which were found to be comparable to that of the antimalarial drug chloroquine (IC50 value 5.2 ng mL−1). Compound 9f, the most active compound found in in vitro studies, provided 40% protection to infected mice at the dose of 96 mg kg−1 × 4 days when screened for its antimalarial activity in vivo against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice by the oral route. In this assay, β-arteether and chloroquine, showed 100% suppression of parasitaemia on day 4 and provided 100% and 80% protection, respectively, to the infected mice.

In Vitro Regulation of Non-enzymatic Antioxidant Efficiency ofMomordica dioica Roxb by Elicitation and Salt Stress

Antioxidants play an important role in inhibiting the free radicals thereby provides protection against infection and degenerative diseases. Natural antioxidants are scavenging reactive oxygen species (ROS), they are preferred over synthetic antioxidants because of their safety over the synthetic antioxidant chemicals. Momordica dioica Roxb., have been used in Indian traditional medicine for various ailments like antiallergic, hepatoprotective , antihyperglycemic, nephroprotective and antimicrobial. In the present investigation sequentially extracts of various plant parts of M. dioica, and its tissue cultures were analyzed for their antioxidant potential. Standard protocols of scavenging effect on the DPPH free radical, Haemoglobin glycosylation Assay, Ferric Reducing Antioxidant Power, Nitric oxide and Lipid Peroxidation Assay were performed with some modifications. The fractionated extractives using different solvents analyzed for their antioxidant potential, the DCF of fruits with DPPH, MF of callus with HG and MF of stem with FRAP assays showed the highest AE. Elicitation increased the AE from 85 to173% in various treated samples. Effect of salt and Vitamin C gave significant blockage that increased with time treatment. Effect of various elicitors (sodium nitroprusside and salicylic acid), ascorbic acid and sodium chloride in different concentrations and time period on AE (antiradical efficiency) was also investigated. Results were expressed as AE, which is 1000/ IC50 in case of DPPH while in FRAP it was expressed as μM/l/g. M. dioica showed that this plant is a potent antioxidant agent. It is able to increase cellular survival by reducing intracellular lipid and protein oxidation levels and ROS scavengers.

An efficient synthesis and biological evaluation of novel analogues of natural product Cephalandole A: A new class of antimicrobial and antiplatelet agents

Cephalandole A 2, a small indole alkaloid isolated from the Taiwanese orchid Cephalanceropsis gracilis (Orchidaceae), exhibits anticancer activity. Surprisingly, this natural product has not been evaluated for any other biological activity so far. To discover other novel potential of Cephalandole A 2, an efficient and economic synthetic protocol for novel Cephalandole A analogues 21a-o has been developed, in only 3 steps from using indole, and applied for their biological activity. Biological testing showed that Cephalandole A 2 and its novel analogues 21a-o exhibited potential antimicrobial and antiplatelet activity in preliminary assay. To the best of our knowledge, this is the first report of Cephalandole A 2 and its novel synthetic analogues 21a-o as a new class of antimicrobial and antiplatelet agents. In this study, 2 and other analogues i.e., 21b, 21d, 21i and 21o showed promising antimicrobial activity against the phytopathogenic bacteria and fungi. Cephalandole A 2, 21c, 21f and 21i, also showed potent antiplatelet activity.

Organocatalytic Modified Guareschi–Thorpe Type Regioselective Synthesis: A Unified Direct Access to 5,6,7,8-Tetrahydroquinolines and Other Alicyclic[b]-Fused Pyridines

An unprecedented organocatalytic, regioselective, modified Guareschi-Thorpe type protocol toward the modular synthesis of 5,6,7,8-tetrahydroquinolines 22a-g and other alicyclic[ b]-fused pyridines 23-28 via the identification of Chitosan as a heterogeneous catalyst is reported. This novel strategy is operationally simple and showed a wide range of functional group tolerance and substrate compatibility. The proposed mechanistic pathway involves an imine-enamine cascade approach for the synthesis of structurally diverse alicyclic[ b]-fused pyridine heterocycles. The gram scale synthesis and identification of a new class of antifungal molecules 29-31 emphasize the practicality of this method.