16-Hydroxy-ent-halima-5(10),13-dien-15,16-olide from Polyalthia longifolia targets adipogenesis by inhibiting mitotic clonal expansion and ameliorates dyslipidemia.

Obesity-related metabolic disorders are increasing at an alarming rate worldwide. The FDA has approved many molecules for weight loss therapy; most of them act on the gut level by inhibiting lipid uptake or on the central nervous system by controlling appetite. Limitations and drawbacks have propelled the search for new pharmacophores exhibiting favourable metabolic alteration at adipocytes, and natural products have always been there to prove their worth. In our efforts, we have identified 16-hydroxy-ent-halima-5(10),13-dien-15,16-olide (PLH), a halimane diterpene isolated from Polyalthia longifolia, demonstrating anti-adipogenic and anti-dyslipidemic activity. It inhibited adipogenesis in 3T3-L1 preadipocyte and C3H10T1/2 mesenchymal stem cell lines. Furthermore, it decreased set of adipogenic markers at transcript and protein levels. Cell cycle studies indicated that PLH halts the mitotic clonal expansion. Mechanistic studies shows that PLH activate Wnt/ß-catenin signaling pathway to inhibit the adipogenesis. The study suggested that PLH inhibited adipogenesis during the early phase of differentiation by targeting mitotic clonal expansion and arresting the cell cycle in the G1 phase of the cell cycle. It improved the dyslipidemic condition in HFD-fed hamsters by decreasing the body weight, fat mass, eWAT weight and improving the serum lipid profile. Overall, PLH has been found as a potential drug candidate and a pharmacophore for combating metabolic disorders including obesity and dyslipidemia.

Netarsudil monotherapy as the initial treatment for open-angle glaucoma and ocular hypertension in Indian patients: A real-world evaluation of efficacy and safety.

Purpose: Glaucoma is the second leading cause of blindness worldwide, affecting more than 64 million people aged 40-80. The best way to manage primary open-angle glaucoma (POAG) is by lowering the intraocular pressure (IOP). Netarsudil is a Rho kinase inhibitor, the only class of antiglaucoma medications that reorganizes the extracellular matrix to improve the aqueous outflow through the trabecular pathway. Methods: An open-label, real-world, multicentric, observation-based 3-month study was performed for assessing the safety and ocular hypotensive efficacy of netarsudil ophthalmic solution (0.02% w/v) in patients with elevated IOP. Patients were given netarsudil ophthalmic solution (0.02% w/v) as a first-line therapy. Diurnal IOP measurements, best-corrected visual acuity, and adverse event assessments were recorded at each of the five visits (Day-1: screening day and first dosing day; subsequent observations were taken at 2 weeks, 4 weeks, 6 weeks, and 3 months). Results: Four hundred and sixty-nine patients from 39 centers throughout India completed the study. The mean IOP at baseline of the affected eyes was 24.84 ± 6.39 mmHg (mean ± standard deviation). After the first dose, the IOP was measured after 2, 4, and 6 weeks, with the final measurement taken at 3 months. The percentage reduction in IOP in glaucoma patients after 3 months of once-daily netarsudil 0.02% w/v solution use was 33.34%. The adverse effects experienced by patients were not severe in the majority of cases. Some adverse effects observed were redness, irritation, itching, and others, but only a small number of patients experienced severe reactions, as reported in a decreasing order: redness > irritation > watering > itching > stinging > blurring. Conclusion: We found that netarsudil 0.02% w/v solution monotherapy when used as the first-line treatment in primary open-angle glaucoma and ocular hypertension was both safe and effective.

Antileishmanial evaluation of triazole-butenolide conjugates: design, synthesis, in vitro screening, SAR and in silico ADME predictions.

In the quest to discover novel scaffolds with leishmanicidal effects, a series of 23 compounds containing the most promising 1,2,3-triazole and highly potent butenolide in one framework were synthesized. The synthesized conjugates were screened against Leishmania donovani parasite; five of them showed moderate antileishmanial activity against promastigotes (IC50 30.6 to 35.5 µM) and eight of them exhibited significant activity against amastigotes (IC50 ≤12 µM). Compound 10u was found to be the most active (IC50 8.4 ± 0.12 µM) with the highest safety index (20.47). The series was further evaluated against Plasmodium falciparum (3D7 strain) and seven compounds were found to be moderately active. Among them, again 10u emerged as the most active compound (IC50 3.65 µM). In antifilarial assays against adult female Brugia malayi, five compounds showed grade II inhibition (50-74%). Structure-activity relationship (SAR) analysis suggested a substituted phenyl ring, triazole and butenolide as essential structural features for bioactivity. Moreover, the results of in silico ADME parameter and pharmacokinetic studies indicated that the synthesized triazole-butenolide conjugates abide by the required criteria for the development of orally active drugs, and thus this scaffold can be used as a pharmacologically active framework that should be considered for the development of potential antileishmanial hits.

Design, synthesis and evaluation of novel pyrrole-hydroxybutenolide hybrids as promising antiplasmodial and anti-inflammatory agents.

In the pursuance of novel scaffolds with promising antiplasmodial and anti-inflammatory activity, a series of twenty-one compounds embraced with most promising penta-substituted pyrrole and biodynamic hydroxybutenolide in single skeleton was designed and synthesized. These pyrrole-hydroxybutenolide hybrids were evaluated against Plasmodium falciparum parasite. Four hybrids 5b, 5d, 5t and 5u exhibited good activity with IC50 of 0.60, 0.88, 0.97 and 0.96 µM for chloroquine sensitive (Pf3D7) strain and 3.92, 4.31, 4.21 and 1.67 µM for chloroquine resistant (PfK1) strain, respectively. In vivo efficacy of 5b, 5d, 5t and 5u was studied against the P. yoelii nigeriensis N67 (a chloroquine-resistant) parasite in Swiss mice at a dose of 100 mg/kg/day for 4 days via oral route. 5u was found to show maximum 100% parasite inhibition with considerably increased mean survival time. Simultaneously, the series of compounds was screened for anti-inflammatory potential. In preliminary assays, nine compounds showed more than 85% inhibition in hu-TNFα cytokine levels in LPS stimulated THP-1 monocytes and seven compounds showed more than 40% decrease in fold induction in reporter gene activity analyzed via Luciferase assay. 5p and 5t were found to be most promising amongst the series, thus were taken up for further in vivo studies. Wherein, mice pre-treated with them showed a dose dependent inhibition in carrageenan induced paw swelling. Moreover, the results of in vitro and in vivo pharmacokinetic parameters indicated that the synthesized pyrrole-hydroxybutenolide conjugates abide by the required criteria for the development of orally active drug and thus this scaffold can be used as pharmacologically active framework that should be considered for the development of potential antiplasmodial and anti-inflammatory agents.

A standardized extract of Coleus forskohlii root protects rats from ovariectomy-induced loss of bone mass and strength, and impaired bone material by osteogenic and anti-resorptive mechanisms.

Introduction: In obese humans, Coleus forskohlii root extract (CF) protects against weight gain owing to the presence of forskolin, an adenylate cyclase (AC) activator. As AC increases intracellular cyclic adenosine monophosphate (cAMP) levels in osteoblasts that has an osteogenic effect, we thus tested the skeletal effects of a standardized CF (CFE) in rats. Methods: Concentrations of forskolin and isoforskolin were measured in CFE by HPLC. CFE and forskolin (the most abundant compound present in CFE) were studied for their osteogenic efficacy in vitro by alkaline phosphatase (ALP), cAMP and cyclic guanosine monophosphate (cGMP) assays. Femur osteotomy model was used to determine the osteogenic dose of CFE. In growing rats, CFE was tested for its osteogenic effect in intact bone. In adult ovariectomized (OVX) rats, we assessed the effect of CFE on bone mass, strength and material. The effect of forskolin was assessed in vivo by measuring the expression of osteogenic genes in the calvarium of rat pups. Results: Forskolin content in CFE was 20.969%. CFE increased osteoblast differentiation and intracellular cAMP and cGMP levels in rat calvarial osteoblasts. At 25 mg/kg (half of human equivalent dose), CFE significantly enhanced calcein deposition at the osteotomy site. In growing rats, CFE promoted modeling-directed bone formation. In OVX rats, CFE maintained bone mass and microarchitecture to the level of sham-operated rats. Moreover, surface-referent bone formation in CFE treated rats was significantly increased over the OVX group and was comparable with the sham group. CFE also increased the pro-collagen type-I N-terminal propeptide: cross-linked C-telopeptide of type-I collagen (PINP : CTX-1) ratio over the OVX rats, and maintained it to the sham level. CFE treatment decreased the OVX-induced increases in the carbonate-to-phosphate, and carbonate-to-amide-I ratios. CFE also prevented the OVX-mediated decrease in mineral crystallinity. Nanoindentation parameters, including modulus and hardness, were decreased by OVX but CFE maintained these to the sham levels. Forskolin stimulated ALP, cAMP and cGMP in vitro and upregulated osteogenic genes in vivo. Conclusion: CFE, likely due to the presence of forskolin displayed a bone-conserving effect via osteogenic and anti-resorptive mechanisms resulting in the maintenance of bone mass, microarchitecture, material, and strength.

Moringa oleifera impedes protein glycation and exerts reno-protective effects in streptozotocin-induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Moringa oleifera is a valued plant with wide distribution in tropical and subtropical regions of the world. It is traditionally used for the treatment of fever, infections, rheumatism, cancer, improving cardiac, renal and hepatic functions, and regulating blood glucose level. The plant has been scientifically reported for the anti-inflammatory, antioxidant, renoprotective, and anti-diabetic properties. Diabetic patients are prone to develop end-stage renal diseases due to incidence of diabetes-induced renal dysfunctions. Given that, increased production and accumulation of advanced glycation end-products (AGEs) play a conspicuous role in the development of diabetes-linked renal dysfunctions, nature-based interventions with AGEs inhibitory activity can prevent renal dysfunctions leading to renoprotection. AIM OF THE STUDY: The study aimed to demonstrate the preventive effects of the ethanolic extract of the leaves of Moringa oleifera (EEMO) on protein glycation and its further assessment for the renoprotective effect in diabetic rats. MATERIALS AND METHODS: Antiglycation activity of EEMO was assessed in vitro using bovine serum albumin. For reno-protective activity assessment, streptozotocin (STZ)-induced diabetic rats were orally treated with EEMO (100 mg/kg) or standard antiglycation agent aminoguanidine (100 mg/kg) for consecutive 8 weeks. The effects on glucose homeostasis, renal functions, and renal morphology were assessed by clinical biochemistry, molecular and histological examination. RESULTS: Presence of EEMO efficiently prevented glucose-, fructose- or methylglyoxal-mediated glycation of protein. Under in vivo set-up, compared to diabetic control rats, EEMO treatment effectively improved the glucose tolerance and body weight, and reduced the serum levels of triglycerides and total cholesterol. Additionally, EEMO administration significantly ameliorated renal dysfunctions in diabetic rats characterized by improved levels of creatinine, urea nitrogen, and uric acid in serum, and total protein level in urine, accompanied by improved kidney morphology. The diabetes-associated pro-inflammatory response characterized by upregulated expression of the inducible nitric oxide synthase (iNos), activation of nuclear factor kappa B (NF-κB) and the raised levels of inflammatory factors, interleukin-1 beta (IL-1ß) and interleukin-6 (IL-6) in renal tissue was significantly attenuated in EEMO-treated rats. Moreover, EEMO treatment diminished renal reactive oxygen species (ROS) levels in diabetic animals. CONCLUSIONS: Our study demonstrated that EEMO prevented AGEs formation and ameliorated renal dysfunctions in diabetic rats by blocking inflammatory/oxidative pathways. Our observations justify M. oleifera as a potential source of therapeutic interventions for diabetic nephropathy management.

A novel BMP2 secretagogue ameliorates glucocorticoid induced oxidative stress in osteoblasts by activating NRF2 dependent survival while promoting Wnt/ß-catenin mediated osteogenesis.

In our previous study, a novel BMP2 secretagogue was synthesized belonging to a class of galloyl conjugates of flavanones, with remarkable osteogenic potential that promoted bone regeneration. We aimed to establish the protective effect of our compound against bone loss that co-exists with excess Glucocorticoid (GC) therapy. GC therapy induces osteoblast damage leading to apoptosis by increasing reactive oxygen species (ROS). Our results delineate that compound 5e (a BMP2 secretagogue) activates NRF2 signalling to counter the disturbed cellular redox homeostasis and escalate osteoblast survival as assessed by Western blot and immunocytochemistry. Depletion of NRF2 by siRNA blocked activation of the NRF2/HO-1 pathway, magnified oxidative stress, increased apoptosis and abrogated the protective effects of compound 5e. 5e, on the other hand, increased ALP, mineralization activity, and promoted osteoblast differentiation by activating WNT/ß-catenin signalling in BMP2 dependent manner, validated by Western blot of WNT3A, SOST, GSK3-ß and ß-catenin nuclear translocation. Treatment of 5e in presence of BMP inhibitor noggin attenuated the osteogenic efficacy and minimized Wnt//ß-catenin signalling in presence of dexamethasone. Our compound prevents GC challenged trabecular and cortical bone loss assessed by micro-CT and promotes bone formation and osteocyte survival determined by calcein labelling and TUNEL assay in GC treated animals. The osteogenic potential of the compound was authenticated by bone turnover markers. On a concluding note, compounds with BMP upregulation can be potential therapeutics for the prevention and treatment of glucocorticoid-induced osteoporosis.

Furostanol saponins from Asparagus racemosus as potential hypoglycemic agents.

Bioactivity guided phytochemical investigation led to isolation of six undescribed furostanol saponins, furoasparoside A-F along with five known compounds, gallic acid, methyl gallate, quercetin-3-O-ß-glucopyranoside, liquiritigenin 4׳-O-ß-apiofuranosyl-(1 â†’ 2)-ß-glucopyranoside and ß-glucogallin for the first time from the roots of Asparagus racemosus. Isolated saponins were screened for their antidiabetic potential in L6-GLUT4myc myotubes in vitro followed by an in vivo evaluation in streptozocin-induced diabetic rats and db/db mice. Furoasparoside E produced a notable decrease in the postprandial blood glucose profile, in leptin receptor-deficient db/db mice, type 2 diabetes model. The effect of furoasparoside E on GLUT4 translocation was found to be mediated by the AMPK-dependent signaling pathway in L6-GLUT4myc myotubes. Moreover, it emerged as a stable plant metabolite with higher bioavailability and efficacy in in vivo pharmacokinetic studies. Therefore, these studies indicated that furoasparoside E may serve as a propitious lead for the management of type 2 diabetes and its secondary complications from natural source.

Antiglycation activity of ß-glucogallin from Asparagus racemosus.

The increased formation and accumulation of advanced glycation end products (AGEs) has been implicated in pathogenesis of various chronic ailments, including diabetes-associated secondary complications, atherosclerosis, aging, inflammatory and neurodegenerative diseases. Therefore, inhibition of AGEs formation is an imperative strategy for alleviating diverse pathologies. Here, we have demonstrated the AGEs inhibitory activity of ß-glucogallin, isolated for the first time from the roots of Asparagus racemosus. ß-glucogallin significantly mitigated fructose-, glucose- and methylglyoxal-induced glycation of bovine serum albumin (BSA). Also, the presence of ß-glucogallin decreased fructosamine and protein carbonyls content, and increased thiol group content in the fructose-BSA system. These activities of ß-glucogallin from Asparagus racemosus underscore its likely pharmacological potential for impeding AGEs-related metabolic disorders.

Blue Sclera as a Complication of Micropulse Transscleral Laser Therapy.

We report 3 patients who underwent micropulse laser therapy for glaucoma and subsequently developed a bluish-black discoloration of the sclera in a semicircular pattern corresponding to the probe path. This complication has not yet been reported with the micropulse laser treatment.

Synthesis and Evaluation of Galloyl Conjugates of Flavanones as BMP-2 Upregulators with Promising Bone Anabolic and Fracture Healing Properties.

The molecular hybridization concept led us to design a series of galloyl conjugates of flavanones that have potent osteoblast differentiation ability in vitro and promote bone formation in vivo. An array of in vitro studies, especially gene expression of osteogenic markers, evinced compound 5e as the most potent bone anabolic agent, found to be active at 1 pM, which was then further assessed for its osteogenic potential in vivo. From in vivo studies on rat calvaria and a fracture defect model, we inferred that compound 5e, at an oral dose of 5 mg/(kg day), increased the expression of osteogenic genes (RUNX2, BMP-2, Col1, and OCN) and the bone formation rate and significantly promoted bone regeneration at the fracture site, as evidenced by the increased bone volume/tissue fraction compared with vehicle-treated rats. Furthermore, structure-activity relationship studies and pharmacokinetic studies suggest 5e as a potential bone anabolic lead for future osteoporosis drug development.

Identification of Natural Products as Potential Pharmacological Chaperones for Protein Misfolding Diseases.

Defective protein folding and accumulation of misfolded proteins is associated with neurodegenerative, cardiovascular, secretory, and metabolic disorders. Efforts are being made to identify small-molecule modulators or structural-correctors for conformationally destabilized proteins implicated in various protein aggregation diseases. Using a metastable-reporter-based primary screen, we evaluated pharmacological chaperone activity of a diverse class of natural products. We found that a flavonoid glycoside (C-10, chrysoeriol-7-O-ß-D-glucopyranoside) stabilizes metastable proteins, prevents its aggregation, and remodels the oligomers into protease-sensitive species. Data was corroborated with additional secondary screen with disease-specific pathogenic protein. In vitro and cell-based experiments showed that C-10 inhibits α-synuclein aggregation which is implicated in synucleinopathies-related neurodegeneration. C-10 interferes in its structural transition into ß-sheeted fibrils and mitigates α-synuclein aggregation-associated cytotoxic effects. Computational modeling suggests that C-10 binds to unique sites in α-synuclein which may interfere in its aggregation amplification. These findings open an avenue for comprehensive SAR development for flavonoid glycosides as pharmacological chaperones for metastable and aggregation-prone proteins implicated in protein conformational diseases.

Flavonoids from Polyalthia longifolia prevents advanced glycation end products formation and protein oxidation aligned with fructose-induced protein glycation.

Advanced glycation end products (AGEs) are reactive chemical entities formed by non-enzymatic reaction between reducing sugars and amino group of proteins. Enhanced accumulation of AGEs and associated protein oxidation contribute to pathogenesis of diabetes-associated complications. Here, we evaluated the inhibitory activity of flavonoid compounds isolated from the leaves of Polyalthia longifolia on formation of AGEs and protein oxidation. Antiglycation activity was determined by measuring the formation of AGE fluorescence intensity, Nε-(carboxymethyl) lysine, and level of fructosamine. Protein oxidation was examined using levels of protein carbonyls and thiol group. Compounds significantly (p < 0.001) restricted the formation of fluorescent AGEs in fructose- BSA and methylglyoxal-BSA systems. Furthermore, there was a decrease in levels of fructosamine and protein carbonyls, and elevation in level of thiol group in fructose-BSA in presence of flavonoids. In summary, flavonoids from Polyalthia longifolia inhibit fructose-mediated protein glycation and oxidation, and can be potential agent for preventing AGE-mediated diabetic complications.

Resurrection of Nalidixic Acid: Evaluation of Water-Based Nanoformulations as Potential Nanomedicine.

Resistance to quinolone antibiotics has been a serious problem ever since nalidixic acid was introduced into clinical medicine. Over time, resistance of pathogenic microbes to nalidixic acid led to the design of novel variants to revive its potential application. In the present work, a series of eight nanoformulations of nalidixic acid-based diacyl and sulfonyl acyl hydrazine derivatives were prepared. All nanoformulations were found to be stable at different storage temperatures. Antibacterial and anticandida activity of the eight nanoformulations presented encouraging results when compared with their non-nano parent counterparts. The nanoformulations of chloro, furanyl, and sulfonyl acyl substituted derivatives of nalidixic acid displayed most promising results (MIC ranging from 50 to 100 µg mL-1) against the tested bacteria and yeast. Among the screened bacteria, Acinetobacter baumannii displayed maximum sensitivity to the above nanoformulations. Biosafety study on the mammalian model-wax moth, Galleria mellonella-showed that all eight prepared nanoformulations were absolutely nontoxic to the larvae and subsequent pupae and hence may likely have no or low toxicity against mammalian systems.

Development and storage study of reduced sugar soy containing compound chocolate.

Possibility of using full fat soy flour (FFSF) for replacer for whole milk powder (WMP), stevia-mannitol blend as replacer for sugar and soybean oil (SBO) as replacer for cocoa butter in chocolate manufacture without impairing the sensory quality characteristics of chocolate was explored. Data on the sensory evaluation of WMP, sugar and cocoa butter substituted chocolates revealed that 40% (w/w) of WMP, sugar and cocoa butter can be successfully substituted by FFSF, stevia-mannitol blend and SBO, respectively in the preparation of high protein and low sugar chocolate without impairing the sensory attributes. Lecithin was found to be optimum at 0.32% (w/w) level of chocolate mix. Protein content of optimized formulation increased by 21.8% over control. Storage study of the product indicated an increase in hardness, free fatty acid content, peroxide value, total plate count, yeast and mold count, whereas a decrease in moisture content, pH value and sensory scores. The optimized chocolate was found acceptable (score ≥7.0) after 90 days of storage at 16 ± 1°C and ~65% RH.

Microwave synthesis and antifungal evaluations of some chalcones and their derived diaryl-cyclohexenones.

Microwave irradiation (MWI) of acetophenones and substituted benzaldehydes in water resulted in a "green-chemistry" procedure for the preparation of chalcones (1-14), through base catalyzed Claisen-Schmidt condensation reaction, in good yields. Further 3,5-diaryl-6-carbethoxy-2-cyclohexen-1-ones (1a-14a) were prepared through base catalyzed cyclocondensation of above chalcones with ethylacetoacetate using MWI as the energy source and silica as support. Out of fourteen cyclohexenones, ten (1a, 4a, 5a, 6a, 7a, 9a, 10a, 11a, 12a and 13a) are reported for the first time in literature. The synthesized compounds were characterized using various spectroscopic techniques, viz. ((1)H NMR and IR) and screened for their antifungal activity in vitro against Sclerotium rolfsii and Rhizoctonia solani by poisoned food technique. The compounds tested were found to be active against R. solani whereas against S. rolfsii, moderate activity was observed, as evident from LC(50) values. The most potent compounds against R. solani were 1-(4-Fluoro-phenyl)-3-phenyl-propenone (13) and 1,3-Diphenyl-propenone (14) having LC(50) values of 2.36 and 2.49 mg L(- 1) respectively (LC(50) of Hexaconazole = 1.12 mg L(- 1)) and against S. rolfsii 3-(4-Fluoro-phenyl)-5-(3-nitro-phenyl)-6-carbethoxy-2-cyclohexen-1-one (12a) was most active having LC(50) value of 285 mg L(- 1)compared to Hexaconazole (LC(50) = 1.27 mg L(- 1)).

Development of controlled release formulations of azadirachtin-A employing poly(ethylene glycol) based amphiphilic copolymers.

Controlled release (CR) formulations of azadirachtin-A, a bioactive constituent derived from the seed of Azadirachta indica A. Juss (Meliaceae), have been prepared using commercially available polyvinyl chloride, polyethylene glycol (PEG) and laboratory synthesized poly ethylene glycol-based amphiphilic copolymers. Copolymers of polyethylene glycol and various dimethyl esters, which self assemble into nano micellar aggregates in aqueous media, have been synthesized. The kinetics of azadirachtin-A, release in water from the different formulations was studied. Release from the commercial polyethylene glycol (PEG) formulation was faster than the other CR formulations. The rate of release of encapsulated azadirachtin-A from nano micellar aggregates is reduced by increasing the molecular weight of PEG. The diffusion exponent (n value) of azadirachtin-A, in water ranged from 0.47 to 1.18 in the tested formulations. The release was diffusion controlled with a half release time (t(1/2)) of 3.05 to 42.80 days in water from different matrices. The results suggest that depending upon the polymer matrix used, the application rate of azadirachtin-A can be optimized to achieve insect control at the desired level and period.

Synthesis and bioefficacy evaluation of new 3-substituted-3,4-dihydro-1,3-benzoxazines.

A new series of 1, 3-Benzoxazines were synthesized, characterized ((1)H NMR and (13)C NMR) and evaluated for their pesticidal activity. Six new 3-alkyl-3, 4-dihydro-4-methyl-2H-1, 3-benzoxazines (1-6) were prepared by hydroxymethylation of secondary amines with formaldehyde in 65-68% yields. These compounds were screened for there IGR activity against Spodoptera litura and for antifungal fungal activity in vitro against Sclerotium rolfsii ITCC 6181 by poisoned food technique. Insect Growth Regulatory (IGR) activity against Spodoptera litura showed that compound 3-Nonyl-3,4-dihydro-4-methyl-2H-1,3-benzoxazines was most effective as IGR with larval GI(50) of 1.863 mu g/Insect. Compounds 3-Octyl-3,4-dihydro-4-methyl-2H-1,3-benzoxazines and 3-Decyl-3,4-dihydro-4-methyl-2H-1,3-benzoxazines were effective IGRs. Antifungal screening revealed that compound 3-Dodecyl-3, 4-dihydro-4-methyl-2H-1,3-benzoxazines, was highly effective against Sclerotium rolfsii with LC(50) value 31.7 mg L(-1) comparable with commercial fungicide Hexaconazole (LC(50) 1.27 mg L(-1)). Also compounds 3-Nonyl-3, 4-dihydro-4-methyl-2H-1,3-benzoxazines and 3-Decyl-3,4-dihydro-4-methyl-2H-1,3-benzoxazines displayed promising fungitoxicity. The results described in this paper are promising and provides new array of synthetic chemicals to be utilized as pesticides.

Synthesis and pesticidal activity of new N-alkyl-N-[1-(2-hydroxyphenyl) ethyl]amines.

A series of novel N-alkyl-N-[1-(2-hydroxyphenyl) ethyl]amines were synthesized as potential new agents to control pests. Their structures were confirmed on the basis of IR, NMR and elemental analyses. Six new N-alkyl-N-[1-(2-hydroxyphenyl) ethyl]amines were prepared by reduction of corresponding Schiff bases using sodium borohydride in 80-87 % yields. These compounds were tested for their antifungal activity against two pathogenic fungi viz., Rhizoctonia bataticola ITCC 0482 and Sclerotium rolfsii ITCC 5226 and for insecticidal activity against insects of stored grain pest Callosobruchus analis. Fungicidal bioassay revealed that compound N-Decyl-N-[1-(2-hydroxyphenyl)ethyl]amine, was highly effective against R. bataticola (ED(50) 6.86 mg L(-1)) which was comparable with that of commercial fungicide hexaconazole (ED(50) 6.35 mg L(-1)). Also compounds N-Heptyl-N-[1-(2-hydroxyphenyl)ethyl]amine, N-Octyl-N-[1-(2-hydroxyphenyl)ethyl]amine and N-Nonyl-N-[1-(2-hydroxyphenyl)ethyl]amine displayed promising fungitoxicity against same pathogen. However, compound N-Heptyl-N-[1-(2-hydroxyphenyl)ethyl]amine was also found to be effective against S. rolfsii (ED(50) 4.92 mg L(-1) as against 1.27 mg L(-1) for hexaconazole). Compound N-Hexyl-N-[1-(2-hydroxyphenyl)ethyl]amine was most effective as insecticide followed by compound N-Octyl-N-[1-(2-hydroxyphenyl)ethyl]amine. LC(50) values for these compounds were 155.0 and 275.0 mg L(-1) respectively as against 36.70 mg L(-1) for commercial insecticide dichlorovos. The results obtained from bioassays indicate that this class of compounds can be utilized for the design of new substances endowed with pesticidal activities.