Zafar Saeed Saify

Synthesis of Coumarin Derivatives with Cytotoxic, Antibacterial and Antifungal Activity

The synthesis and selective biological screening of 7-hydroxy-4-methyl-2H-chromen-2-one (2), 7-hydroxy-4,5-dimethyl-2H-chromen-2-one (15) and some of their derivatives were carried out. Compound 13 was found to be most potent cytotoxic agent with LD50 = 126.69 μg/ml. In antibacterial assay the compounds showed a broad spectrum of activities. Compound 11 exhibited a very high degree of plant growth inhibition at three levels of concentration. Compound 4 showed very promising antifungal activity against Candida albicans. Compounds 12 and 13 demonstrated excellent antioxidant activity.

Naturally occurring and synthetic agents as potential anti-inflammatory and immunomodulants.

Terpenes in general and triterpenes in particular showed anti-inflammatory activity and act as immunomodulators in nutraceutical agents. Antiinflammation, a useful and attractive approach in experimental oncology, helps to investigate the inflammation preventive potential of natural products and synthetic entities. During the course of our research work in natural product chemistry and synthesis of novel structures in the field of heterocyclic chemistry, we found interesting results. In natural product betulinic acid, α-amyrin acetate, lupeol acetate, oleanolic acid, ursolic acid and their derivatives showed interesting potential analgesic and anti-inflammatory activity. In this review specific reference has been made to novel classes and newly discovered compounds in the literature, which exhibited required activities. Indomethacine is a potent synthetic compound, which becomes the basis of novel anti-inflammatory agents. Shen postulated a receptor theory which indicates the physical parameters responsible for anti-inflammatory activity. Attempt has been made to cover almost all the anti-inflammatory agents which fall under the various chemical structural classes of compounds showing required activity. The objective of this review is to compile relevant data on the mechanism of action of terpenes isolated from active ethnomedicinal plants to examine the role terpenoids have in medicinal plants used against inflammatory diseases, especially those in which an immune response is implicated. In addition, a selection of several structurally related compounds has been compiled in order to analyze the possible structural characteristics and relationships between the different types of structures found in triterpenoids. The selection of active species was made on the basis of their immunomodulatory activity, and their role in the resolution of diseases in which the immune system is implicated to examine the mechanism by which they are useful as ethnopharmacological medicines. These terpenes include ursolic acid, oleanolic acid, betulinic acid. This review discusses in detail the preclinical studies conducted with triterpenes and provides an insight into its mechanism of action.

Malaria and artemisinin derivatives: an updated review.

Malaria is the worlds most prevalent disease that affects 515-600 million people each year and about 40% of the worlds population live at risk for this infection. The prevalence of morbidity and mortality from drug resistant malaria (Plasmodium falciparum) is increasing in most of the developing countries, which is also a global threat because international travel is common now and imported malaria is increasingly a serious problem. Since rapid schizonticidal action of naturally occurring endoperoxides pharmacophore present in artemisinin against drug-resistant malaria has been documented, researchers have focused more on artemisinin analogs than any other antimalarials. In this review, drugs of choice about malaria i.e. artemisinin and its analogus/derivatives (arteether, artemether, artemiside, artemisinin, artemisone, artesunate, dihydroartemisinin) have been discussed in detail e.g. bioavailability, formulation development, stability, combination therapy, additional benefits, drug resistance and toxicity have been reviewed.

Triterpenes, A sterol and A monocyclic alcohol from Momordica charantia

Abstract Five new compounds have been isolated from the fresh fruits of Momordica charantia and their structures elucidated through spectroscopic studies. These include three pentacyclic triterpenes 13-hydroxy-28-methoxy-urs-11-en-3-one (momordicin), 13β,28-epoxy-urs-11-en-3-one (momordicinin), 24-[1′-hydroxy,1′-methyl-2′-pentenyloxyl]-ursan-3-one (momordicilin), a sterol 3β-hydroxy-stigmasta-5,14-dien-16-one (momordenol) and a monocyclic alcohol 1-hydroxy-1,2-dimethyl-2-[8′,10′-dihydroxy-4′,7′-dimethyl-11′-hydroxy methyl-trideca]-3-ethyl-cyclohex-5-en-4-one (momordol).

Pre- and postsynaptic responses to 1-(1-naphthylpiperazine) following adaptation to stress in rats.

In view of a role of pre- and postsynaptic serotonin (5-hydroxytryptamine; 5-HT) receptors in adaptation to stress, effects of 1-(1-naphthylpiperazine) (1-NP) were compared in unrestrained and repeatedly restrained adapted rats. In the first part of the study, effects of various doses (1.0-15 mg/kg ip) of 1-NP were monitored on brain 5-HT metabolism (presynaptic response) and on the activity (postsynaptic response) of rats in an activity cage to which the rats were habituated before the drug administration. The drug injected at doses of 2.5-15.0 mg/kg increased motor activity and decreased brain 5-hydroxyindoleacetic acid (5-HIAA) concentration in a dose-dependent manner. In the second part of the study, rats were restrained on wire grids 2 h/day for 5 days. First-day episode of 2-h restraint decreased 24-h cumulative food intake, water intake and growth rate. The decreases attenuated following second-, third- and fourth-day episodes of 2-h restraint were not observed following fifth-day episode of 2-h restraint stress, suggesting adaptation to the stress schedule has occurred. Serotonergic and motor responses to 1-NP in unrestrained and repeatedly restrained adapted rats were compared by injecting the drug at a dose of 5 mg/kg, a dose that above results suggested would not produce maximal effects on 5-HT metabolism or motor activity. Administration of 1-NP at a dose of 5 mg/kg increased motor activity and decreased brain 5-HIAA concentration in unrestrained and repeatedly restrained adapted rats. Increases of motor activity were much greater in repeatedly restrained adapted than unrestrained rats. Decreases of 5-HIAA concentration were comparable in the two groups. The results are discussed in the context of an increase in the effectiveness of postsynaptic 5-HT-1A and 5-HT-1B receptors and a decrease in the effectiveness of presynaptic 5-HT-1A (somatodendritic) and 5-HT-1B (terminal) receptors following adaptation to stress. It is suggested that these changes of receptor responsiveness might help coping with stress demand to produce adaptation to stress.

Leishmanicidal potential of N-substituted morpholine derivatives: synthesis and structure-activity relationships.

A series of N-substituted morpholines 2–20 was synthesised by reacting various acid chlorides and alkyl halides with morpholine (1). All of the synthesised compounds 2–20 were screened for their leishmanicidal effects using amphotericin B (IC50 = 0.24 µg L−1) and pentamidine (IC50 = 2.56 µg mL−1) as standards and a structure–activity relationship (SAR) study was established. The compounds 2 (IC50 = 48 µg mL−1), 3 (IC50 = 30.0 µg mL−1), 10 (IC50 = 41.0 µg mL−1), 15 (IC50 = 33.0 µg mL−1), 16 (IC50 = 35.0 µg mL−1) and 20 (IC50 = 47.0 µg mL−1) showed weak leishmanicidal activities.

Synthesis and Biological Screening of 7-Hydroxy-4-Methyl-2 H -Chromen-2-One, 7-Hydroxy-4,5-Dimethyl-2 H -Chromen-2-One and their Some Derivatives

7-Hydroxy-4-methyl-2 H -chromen-2-one (2) , 7-hydroxy-4,5-dimethyl-2 H -chromen-2-one (15) and their some derivatives were synthesized for exploring selected biological screening. The compounds 9 and 13 had shown high degree of cytotoxic activity. Three compound 9 , 10 and 13 showed high degree of bactericidal activity amongst the present series.

Piperidines: A new class of Urease inhibitors

A variety of piperidines (2–12, 14–26) with variable substituents at N-atoms have been synthesized and evaluated as urease inhibitors. The synthesized compounds showed varying degree of urease inhibitory activity ranging from 31.97 to 254 μM. The size and electron-donating or -withdrawing effects of substituents influence the activity, which lead to the formation of urease inhibitors.

Synthesis of 4-hydroxypiperidine derivatives and their screening for analgesic activity.

Six substituted phenacyl derivatives of 4-hydroxypiperidine were prepared and their structures were confirmed through spectroscopic techniques. These newly synthesized derivatives were also screened for analgesic activity by chemical and thermal methods. Only halogenated phenacyl derivatives demonstrated more or less protection against acetic acid induced writhing in mice where as rest of three derivatives were found inactive when screened by this chemical method. Similarly all the six derivatives were proved inactive by tail flick test.

Enzymatic biotransformation of terpenes as bioactive agents.

The plant-derived terpenoids are considered to be the most potent anticancer, anti-inflammatory and anticarcinogenic compounds known. Enzymatic biotransformation is a very useful approach to expand the chemical diversity of natural products. Recent enzymatic biotransformation studies on terpenoids have resulted in the isolation of novel compounds. 14-hydroxy methyl caryophyllene oxide produced from caryophyllene oxide showed a potent inhibitory activity against the butyryl cholinesterase enzyme, and was found to be more potent than parent caryophyllene oxide. The metabolites 3β,7β-dihydroxy-11-oxo-olean-12-en-30-oic acid, betulin, betulonic acid, argentatin A, incanilin, 18β glycyrrhetinic acid, 3,11-dioxo-olean-12-en-30-oic acid produced from 18β glycyrrhetinic acid were screened against the enzyme lipoxygenase. 3,11-Dioxo-olean-12-en-30-oic acid, was found to be more active than the parent compound. The metabolites 3β-hydroxy sclareol 18α-hydroxy sclareol, 6α,18α-dihydroxy sclareol, 11S,18α-dihydroxy sclareol, and 1β-hydroxy sclareol and 11S,18α-dihydroxy sclareol produced from sclareol were screened for antibacterial activity. 1β-Hydroxy sclareol was found to be more active than parent sclareol. There are several reports on natural product enzymatic biotransformation, but few have been conducted on terpenes. This review summarizes the classification, advantages and agents of enzymatic transformation and examines the potential role of new enzymatically transformed terpenoids and their derivatives in the chemoprevention and treatment of other diseases.