Nafees Ahmed

Synthesis and anti-HIV activity of alkylated quinoline 2,4-diols

Naturally occurring quinolone alkaloids, buchapine (1) and compound 2 were synthesized as reported in literature and evaluated for anti-HIV potential in human CD4+ T cell line CEM-GFP, infected with HIV-1(NL4.3) virus by p24 antigen capture ELISA assay. The compounds 1 and 2 showed potent inhibitory activity with IC(50) value of 2.99 and 3.80microM, respectively. Further, 45 alkylated derivatives of quinoline 2,4-diol were synthesized and tested for anti-HIV potential in human CD4+ T cell line CEM-GFP. Among these, 13 derivatives have shown more than 60% inhibition. We have identified three most potent inhibitors 6, 9 and 23; compound 6 was found to be more potent than lead molecule 1 with IC(50) value of 2.35microM and had better therapeutic index (26.64) as compared to AZT (23.07). Five derivatives 7, 19a, 19d, 21 and 24 have displayed good noticeable anti-HIV activity. All active compounds showed higher CC(50) values which indicate that they have better therapeutic indices.

Synthesis and evaluation of β-carboline derivatives as inhibitors of Human Immunodeficiency Virus

A series of beta-carboline derivatives were synthesized by utilizing aromatization and chemoselective alkylation method recently reported from our laboratory. Synthesized derivatives were evaluated for anti-HIV activity in human CD4+ T cell line (CEM-GFP) infected with HIV-1 NL(4.3) virus. 1-Formyl-beta-carboline-3-carbxylic acid methyl ester (15) showed inhibition of human immunodeficiency virus at IC(50)=2.9 microM.

Anti-HIV activity of Indian medicinal plants

Acquired immunodeficiency syndrome patients face great socio-economic difficulties in obtaining treatment. There is an urgent need for new, safe, and cheap anti-HIV agents. Traditional medicinal plants are a valuable source of novel anti-HIV agents and may offer alternatives to expensive medicines in future. Various medicinal plants or plant-derived natural products have shown strong anti-HIV activity and are under various stages of clinical development in different parts of the world. The present study was directed towards assessment of anti-HIV activity of various extracts prepared from Indian medicinal plants. The plants were chosen on the basis of similarity of chemical constituents with reported anti-HIV compounds or on the basis of their traditional usage as immunomodulators. Different extracts were prepared by Soxhlet extraction and liquid–liquid partitioning. Ninety-two extracts were prepared from 23 plants. Anti-HIV activity was measured in a human CD4+ T-cell line, CEM-GFP cells infected with HIV-1NL4.3. Nine extracts of 8 different plants significantly reduced viral production in CEM-GFP cells infected with HIV-1NL4.3. Aegle marmelos, Argemone mexicana, Asparagus racemosus, Coleus forskohlii, and Rubia cordifolia demonstrated promising anti-HIV potential and were investigated for their active principles.

Synthesis and biological evaluation of tricyclic guanidine analogues of batzelladine K for antimalarial, antileishmanial, antibacterial, antifungal and anti-HIV activities.

Fifty analogues of batzelladine K were synthesized and evaluated for in vitro antimalarial (Plasmodium falciparum), antileishmanial (Leishmania donovani), antimicrobial (panel of bacteria and fungi), antiviral (HIV‐1) activities. Analogues 14h and 20l exhibited potential antimalarial activity against chloroquine‐sensitive D6 strain with IC50 1.25 and 0.88 μm and chloroquine‐resistant W2 strain with IC50 1.64 and 1.07 μm, respectively. Analogues 12c and 14c having nonyl substitution showed the most potent antileishmanial activity with IC50 2.39 and 2.78 μm and IC90 11.27 and 12.76 μm, respectively. Three analogues 12c, 14c, and 14i were the most active against various pathogenic bacteria and fungi with IC50 < 3.02 μm and MIC/MBC/MFC <6 μm. Analogue 20l having pentyl and methyl substituents on tricycle showed promising activities against all pathogens. However, none was found active against HIV‐1. Our study demonstrated that the tricyclic guanidine compounds provide new structural class for broad spectrum activity.

Ajwain (Trachyspermum ammi L.) Oils

Abstract Trachyspermum ammi (L.)—commonly known as ajwain or caraway—is native to Egypt and widely grown all over Iraq, Iran, Afghanistan, Pakistan, and India. The seeds of T. ammi (L.) are widely used in India and eastern Asia, both in diet and in traditional medicine. They contain fiber (11.9%), carbohydrates (38.6%), tannins, glycosides, moisture (8.9%), protein (15.4%), fat (18.1%), saponins, flavone, and mineral matter (7.1%). Essential oil prepared from seeds contains thymol (50–60%), γ-terpinene, and p -cymene, along with α- and β-pinenes, α-thujen, myrcene, 1,8-cineole, and carvacrol. Ajwain is an important commercial plant due to its essential oil, which is used in the flavor/food industries. Ajwain oil contributes to a wide range of medicinal applications, such as antibacterial, antifungal, anti-inflammatory, antioxidant, antibacterial, cytotoxic, antilithiasis, nematicidal, anthelmintic, and antifilarial activities. Its seeds exhibit remarkable digestive and antiseptive properties and are used in traditional medicine, primarily to control bowel disorders such as indigestion, flatulence, colic, and diarrhea. They are also used as a stimulant, stomachic, carminative, aromatic, antispasmodic, antihypertensive, antiseptic, antiparasitic, antiscorbutic, antihistamine, vermicide, emmenagogue, and sialagogue. The ajwain oil components, thymol and carvacrol, have attributes for antibacterial and antifungal action against wide range of microbes. This distinctive contribution by ajwain oil components makes it a good food preservative candidate to prevent food spoilage caused by bacteria and fungi.

Myrtle (Myrtus communis L.) Oils

Abstract In the movement to decrease the use of chemical food preservatives, the most promising currently available alternatives are essential oil-based food preservatives. Aromatic plants produce volatile compounds contained in essential oils. These nonnutritional molecules exert a wide range of effects, including antibacterial, antifungal, and antioxidant effects. Their high biodegradability, medicinal importance, and low toxicity to mammals give essential oils important advantages compared with chemical preservatives. Myrtus communis is an aromatic evergreen perennial shrub or small tree, with small foliage and deep fissured bark. It is native to Southern Europe, North Africa, and West Asia. It is distributed in South America, North western Himalaya, and Australia and widespread in the Mediterranean region. Myrtus species have been reported as very rich in volatile oils, phenolic acids, flavonoids, tannins, anthocyanin pigments, and fatty acids. Myrtle essential oil compounds classified into three main categories: terpenes (monoterpene and sesquiterpene hydrocarbons), terpenoids (oxygenated monoterpenes and sesquiterpenes), and phenylpropanoids. The antibacterial properties of myrtle essential oils and extracts against pathogenic bacteria were reported in many studies and obtained results are promising. The myrtle antifungal effect may also be attributed to essential oil and phenolic compounds that are known to cause cell membrane damage, causing leakage of cellular materials and ultimately the death of the microorganism. Several reports describe the antioxidant activities of different extracts and compounds obtained from myrtle leaves and other parts. In this chapter, various qualities of myrtle extracts and essential oils, such as antibacterial, antifungal, and antioxidant properties with respect to food, are summarized. These properties are attributed to the chemical constituents of the essential oil and extracts. The scientific information in this chapter is interpolated and correlated for the possibility of using myrtle essential oil in food preservation.

Synthesis, biological evaluation and molecular docking studies of tricyclic guanidine derivatives for anti-malarial activity

Abstract Introduction Malaria is the most lethal among the parasitic diseases and challenge for developing counties. Globally, an estimated 3.3 billion people were at risk of malaria in 2011, with populations living in sub-Saharan Africa having the highest risk of acquiring malaria. Malarial infection caused by P. falciparum is the most deadly form among all pathogens. Moreover, there has been rapid increase in resistance to drugs by P. falciparum. This resistance is considered because of emergence through mutation or biochemical changes in the active site of drug targets. The lactate dehydrogenase of P. falciparum (PfLDH) has been used since long time as a potential molecular drug target for malaria. The LDH plays role in the inter-conversion of pyruvate to lactate in the glycolysis cycle, which is required for energy production in living cells. Objectives 1) Synthesis of tricyclic guanidine derivatives and biological evaluation against resistant strain of P. falciparum (Lactate Dehydrogenase Inhibitor). 2) Molecular docking of synthesized derivatives to understand mechanism of inhibition. Methods We have synthesized fifty tricyclic guanidine derivatives based on batzelladine K backbone. All synthesized compounds were evaluated for anti-malarial activity against chloroquine resistant strains of P. falciparum by using plasmodial LDH activity as measure of inhibition. To understand the mechanism of inhibition and to identify pharmacophore required for activity, the molecular docking of tricyclic guanidine compounds was performed using CDOCKER program in Discovery Studio suit 3.5. Results & Discussion We have obtained many potent inhibitors. The docking studies showed that there is very strong correlation between in silico and in vitro results. The most active compound was found to have least CDOCKER interaction energy (–43.25 kcal/mol). It showed hydrophobic interaction with Gly27, Ala98, Asp53 and Ile54 residues in the enzyme binding pocket similar to that of chloroquine. Conclusion The synthesized derivatives are potent inhibitor of chloroquine-resistant PfLDH and act on same binding site to that of chloroquine. Based on these results, more potent inhibitor against P. falciparum can be designed.

Bitter Orange ( Citrus aurantium L.) Oils

Abstract The chemico-physical and composite characteristics of food and food products make them susceptible to microbial spoilage. Additives of CO2 in food products such as soft drinks can reduce growth of some microorganisms and induce others. Thermal treatments, to which ingredients and intermediate and final products can be subjected, affect the stability of these products. Since polyethylene terephthalate packaging cannot be thermally treated due the susceptibility of plastic material to heating, food and beverage stability relies upon the addition of preservatives, generally weak acids, such as sorbic and benzoic acids. New strategies for the stabilization of food free from traditional preservatives are constantly being investigated by the manufacturers. In fact, consumers are inclined to consider these preservatives as extraneous and unsafe because they have no connection with the food matrix. Furthermore preservatives could undergo chemical transformations giving origin to toxic compounds. In this scenario, the search for new strategies and new antimicrobials for stabilization of food and beverages has become a central goal for producers. Aromatic compounds and essential oils are an interesting alternative. However, their organoleptic impact and the variable composition of the essential oils (which can be reflected in their antimicrobial activity) limit the industrial use of these substances as preservatives. Furthermore, a stabilization strategy without the addition of excessive concentrations of the flavoring agent seems to be difficult to be realized. Bitter orange oils are obtained from different parts (peels, leaves, and flowers) of Citrus aurantium species. The most abundant component of the bitter oil is the monoterpene limonene that represents 65–97% of the oil, depending on several factors, mainly the extraction method, harvesting time of the plant material, and mainly the geographic origin of the oil. Bitter oil has been reported to possess various pharmacological properties. In this chapter, the antispoilage, antibacterial, antifungal, antioxidant, and flavoring property of bitter orange oil (C. aurantium species) for food preservation are discussed.

Saffron Crocus (Crocus sativus) Oils

Abstract Many studies have demonstrated the potential use of essential oils as food preservatives to help extend the shelf life of food products. Essential oil is proven to be active against a broad spectrum of antimicrobials, including both Gram-positive and Gram-negative bacteria. Additionally, the antifungal and antioxidant qualities of essential oil make it suitable for replacing synthetic preservatives. Saffron oil is one of the essential oil with food preservation qualities. Saffron crocus is indigenous to southwest Asia and is cultivated in Western Asia, Turkey, Iran, Greece, India, and Spain. Saffron oil is one of the most important and costliest oils in the world. Saffron oil is extracted mainly from the flowers and stigma. The major components of saffron essential oil are safranal (responsible for aroma), picrocrocin (bitter taste), and crocin (responsible for color), along with other carotenoids and terpenes. In this chapter, the antibacterial, antifungal, and antioxidant properties of saffron oil are discussed for its use in the food industry.

Jasmine (Jasminum sambac L., Oleaceae) Oils

Abstract An ideal food preservative should ensure that foods and food products remain safe and unspoiled. Essential oil as whole or its components can contribute in the prevention of food spoilage. The potency of naturally occurring antimicrobial agents or essential oil from plants varies from species to species. To achieve the goal of preservation using natural compounds/extracts/essential oils can be done by combining essential oil or its components from various species. Since an ideal agent should ensure the complete protection from food spoilage, mode of action, synergistic and antagonistic effects of the agent have to be considered. In this chapter, the potential value of jasmine essential oil for its antibacterial, antifungal, and antioxidant action is discussed for food preservation. Apart from other uses of jasmine essential oil, it has been found to be active against various gram-negative, gram-positive bacteria and fungi. This property of jasmine oil allows it to be used in food preservation. It also possesses antioxidant activity. The major components of jasmine essential oil are linalool, benzyl acetate, and benzyl benzoate. The linalool is a monoterpeniod alcohol also found in other antimicrobial essential oils. The antimicrobial activity of most terpenoids is linked to their functional groups, and it has been shown that the hydroxyl group of phenolic terpenoids and the presence of delocalized electrons are important for the antimicrobial activity. The mode of action of linalool is associated with membrane expansion, increased membrane fluidity and permeability, disturbance of membrane-embedded proteins, inhibition of respiration, and alteration of ion transport processes of microorganisms. Synergistic antimicrobial effect has been observed for linalool when combined with other groups of monoterpenoids, that is, phenolic monoterpenoid. Various regulatory bodies such as the European commission and US Food and Drug Administration have registered linalool to be a safe flavoring agent used for food products.