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    Smart spectrophotometric method development for simultaneous estimation of antidiabetic drugs in formulations
    (EManuscript Technologies, 2022-01-12) Attimarad, Mahesh; Venugopala, Katharigatta Narayanaswamy; Shafi, Sheeba; Balgoname, Abdulmalek Ahmed; Altaysan, Abdulrahman Ibrahim
    An anti-diabetic formulation consisting of vildagliptin and remogliflozin was prescribed for better glycemic control. In the present study a simple, rapid derivative spectrophotometric methods were evolved to analyze these two analytes from the formulations. Methods: Two processed UV spectrophotometric methods were established by measuring the peak amplitude at zero-crossing of second derivative spectra of analytes. The second procedure comprehends the generation of zero - order spectra from the mixture of analyte spectra by division and multiplication by the pure analyte spectra to remove the effect of one of the analytes. Results: Both methods showed linearity concentrations in the range of 2-75 µg/ml for RGF and 2-50 µg/ml for VGT. The low LOD and LOQ found for RGF and VGT by both methods indicated the good sensitivity of the methods. The mean percentage recovery was 98.60 % and 100.78%, for RGF and 98.81 % and 99.15 % for VGT, with low percent relative error. The % RSD for intra and inter-day precision was less than ±2%. Finally, the planned methods were employed for the assay of the VGT and RGF from the medicine and the outcomes were matched with the reported methods. Conclusion: The assay results of the formulation were in agreement with the concentration of labeled amount and no significant difference was observed in the results when compared to the reported method. Hence, the anticipated procedures could be applied for the routine quality control of formulations consisting of VGT and RGF.
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    Coumarin containing hybrids and their pharmacological activities
    (Phytochemistry & Organic Synthesis Laboratory, 2021-08-09) Kasumbwe, Kabange; Saheed, Sabiu; Makhanya, Talent R.; Venugopala, Katharigatta Narayanaswamy; Mohanlall, Viresh
    Coumarin moiety is of great interest to both chemists and biologists as it is present in a wide variety of naturally occurring bioactive compounds. Studies have lent scientific credence to the biological activities of several coumarin derivatives. The broad spectrum of biological activities linked with coumarin includes antibacterial, antimycobacterial, antioxidant, anticancer, antifungal, anti-inflammatory, anticoagulant and antiviral properties. The electron releasing and withdrawing substituent of coumarin affects the pharmacological properties of its resulting derivatives. Thus, identifying key structural features within the coumarin family is vital to the design and development of new analogues with enhanced pharmacological activity due to the variability in the structural complexity of coumarin. This article presents an up-to-date synopsis on the synthesis of coumarin derivatives and their pharmacological properties.
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    Experimental design approach for quantitative expressions of simultaneous quantification of two binary formulations containing remogliflozin and gliptins by RP-HPLC
    (MDPI AG, 2022) Attimarad, Mahesh; Venugopala, Katharigatta Narayanaswamy; Nair, Anroop Balachandran; Sreeharsha, Nagaraja; Deb, Pran Kishore
    The aim of this study was to develop a fast RP-HPLC method for simultaneous measurement of two antidiabetic formulations (vildagliptin + remogliflozin and teneligliptin + remogliflozin) under identical experimental conditions. Using the Box–Behnken approach and response surface design, the interaction and quadratic influence of three variable parameters, acetonitrile %, pH of the mobile phase, and flow rate, on resolution between the peaks were optimized. To forecast the resolution of peaks (2.7 and 6.5) for the three anti-diabetic medications, the design space with desirability function was used to find the optimal chromatographic conditions. Isocratic elution with 58:42 acetonitrile and phosphate buffer (20 mM KH2PO4, pH adjusted to 4.9 with orthophosphoric acid) over a Zorabx C18 HPLC column with a flow rate of 1.2 mL min−1 separated all three analytes in 2.5 min. In addition, the optimized HPLC process was validated using ICH recommendations. The devised HPLC method’s precision and accuracy were proven by the low percent relative standard deviation (0.60–1.65%), good percentage recovery (98.18–101.50%), and low percentage relative errors (0.20–1.82%). The method’s robustness was also proven by slightly varying the five separate parameters. Finally, the accuracy of the proposed HPLC approach was confirmed using a standard addition method for simultaneous determination of vildagliptin + remogliflozin and teneligliptin + remogliflozin from formulations. Furthermore, the findings demonstrated that experimental design can be successfully used to optimize chromatographic conditions with fewer runs. The devised HPLC method for simultaneous quantification of two binary combinations utilizing the same chromatographic conditions is fast, accurate, precise, and easy, and it might be utilized in laboratories for routine quality control investigations on both formulations.
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    Larvicidal Activities of 2-Aryl-2,3-Dihydroquinazolin-4-ones against Malaria Vector Anopheles arabiensis, in Silico ADMET prediction and molecular target investigation
    (MDPI, 2020-03-02) Venugopala, Katharigatta Narayanaswamy; Ramachandra, Pushpalatha; Tratrat, Christophe; Gleiser, Raquel M.; Bhandary, Subhrajyoti; Chopra, Deepak; Morsy, Mohamed A.; Aldhubiab, Bandar E.; Attimarad, Mahesh; Nair, Anroop B.; Sreeharsha, Nagaraja; Venugopala, Rashmi; Deb, Pran Kishore; Chandrashekharappa, Sandeep; Khalil, Hany Ezzat; Alwassil, Osama I.; Abed, Sara Nidal; Bataineh, Yazan A.; Palenge, Ramachandra; Haroun, Michelyne; Pottathil, Shinu; Girish, Meravanige B.; Akrawi, Sabah H.; Mohanlall, Viresh
    Malaria, affecting all continents, remains one of the life-threatening diseases introduced by parasites that are transmitted to humans through the bites of infected Anopheles mosquitoes. Although insecticides are currently used to reduce malaria transmission, their safety concern for living systems, as well as the environment, is a growing problem. Therefore, the discovery of novel, less toxic, and environmentally safe molecules to effectively combat the control of these vectors is in high demand. In order to identify new potential larvicidal agents, a series of 2-aryl-1,2-dihydroquinazolin-4-one derivatives were synthesized and evaluated for their larvicidal activity against Anopheles arabiensis. The in silico absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties of the compounds were also investigated and most of the derivatives possessed a favorable ADMET profile. Computational modeling studies of the title compounds demonstrated a favorable binding interaction against the acetylcholinesterase enzyme molecular target. Thus, 2-aryl-1,2-dihydroquinazolin-4-ones were identified as a novel class of Anopheles arabiensis insecticides which can be used as lead molecules for the further development of more potent and safer larvicidal agents for treating malaria.
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    An efficient, lung-targeted, drug-delivery system to treat asthma via microparticles
    (Dove Medical Press, 2019-12-27) Nagaraja, SreeHarsha; Venugopala, Katharigatta Narayanaswamy; Anroop, Nair; Roopashree, Srinivasa; Mahesh, Attimarad; Jagadeesh, Hiremath; Bandar, Al-Dhubiab; Chandramouli, Ramnarayanan; Pottathil, Shinu; Mukund, Handral; Micheline, Haroun; Christophe, Tratrat
    Background: Chronic diseases such as diabetes, asthma, and heart disease are the leading causes of death in developing countries. Public health plays an important role in preventing such diseases to improve individuals’ quality of life. Conventional dosage schemes used in public health to cure various diseases generally lead to undesirable side effects and renders the overall treatment ineffective. For example, a required concentration of drug cannot reach the lungs using conventional methods to cure asthma. Microspheres have emerged as a confirmed drug-delivery system to cure asthma. Method: In this paper, a salbutamol-loaded poly lactic acid-co-glycolic acid-polyethylene glycol (PLGA-PEG) microsphere (SPP)-based formulation was prepared using a Buchi B-90 nanospray drier. Face-centered central composite design (CCD) was applied to optimize the spray-drying process. Results: The drug content and product yield were found to be 72%±0.8% and 86%±0.4%, respectively; drug release (91.1%) peaked for up to 12 hrs in vitro. Microspheres obtained from the spray dryer were found to be shriveled. The experiments were carried out and verified using various groups of rabbits. In our study, the particle size (8.24 μm) was observed to be an essential parameter for drug delivery. The in vivo results indicated that the targeting efficacy and drug concentration in the lung was higher with the salbutamolloaded PLGA-PEG SPP formulation (1,410.1±10.11 μg/g, 15 mins), as compared to the conventional formulation (92±0.56 μg/g, 10 min). The final product was stable under 5°C±2°C, 25°C±2°C, and 40°C±2°C/75%±5% relative humidity. In addition, these co-polymers have a good safety profile, as determined by testing on human alveolar basal epithelium A549 cell lines. Conclusion: Our results prove that microspheres are an alternative drug-delivery system for lung-targeted asthma treatments used in public health.
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    International Union of Crystallography
    (Crystal structure of methyl 4-(4-hydroxyphenyl)-6- methyl-2-oxo-1,2,3,4-tetrahydropyrimidine-5- carboxylate monohydrate, 2016-08-19) Bairagi, Keshab M.; Venugopala, Katharigatta Narayanaswamy; Mondal, Pradip Kumar; Odhav, Bharti; Nayak, Susanta K.
    The title hydrate, C13H14N2O4H2O, crystallizes with two formula units in the asymmetric unit (Z0 = 2). The dihedral angles between the planes of the tetrahydropyrimidine ring and the 4-hydroxyphenyl ring and ester group are 86.78 (4) and 6.81 (6), respectively, for one molecule and 89.35 (4) and 3.02 (4) for the other. In the crystal, the organic molecules form a dimer, linked by a pair of N—HO hydrogen bonds. The hydroxy groups of the organic molecules donate O—HO hydrogen bonds to water molecules. Further, the hydroxy group accepts N—HO hydrogen bonds from amides whereas the water molecules donate O—HO hydrogen bonds to the both the amide and ester carbonyl groups. Other weak interactions, including C—HO, C—H and –, further consolidate the packing, generating a three-dimensional network.
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    Silica-sulfuric acid : novel, simple, efficient and reusable catalyst for hydration of nitrile to amide
    (Asian Publication Corporation, 2016) Chandrashekharappa, Sandeep; Venugopala, Katharigatta Narayanaswamy; Venugopala, Rashmi; Odhav, Bharti
    Silica-sulfuric acid efficiently catalyzes conversion of aliphatic, substituted aromatic and hetero aromatic nitriles to their corresponding amides in good to excellent yields under reflux condition. Products obtained were purified by column chromatography method and characterized by ¹H NMR, ¹³C NMR and mass spectral analysis.
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    Antimycobacterial, docking and molecular dynamic studies of pentacyclic triterpenes from Buddleja saligna leaves
    (Taylor and Fancis Online, 2017) Singh, Alveera; Venugopala, Katharigatta Narayanaswamy; Khedr, Mohammed A.; Pillay, Mellendran; Nwaeze, Kenneth U.; Coovadia, Yacoob; Shode, Francis; Odhav, Bharti
    Buddleja saligna (family Buddlejaceae) is a medicinal plant endemic to South Africa. Two isomeric pentacyclic triterpenes, oleanolic acid and ursolic acid, were isolated from the leaves of B. saligna using silica gel column chromatography. Compounds oleanolic acid and ursolic acid were subjected to derivatization with acetic anhydride in the presence of pyridine to obtain oleanolic acid-3-acetate and ursolic acid-3-acetate, respectively. The structures of these compounds were fully characterized by detailed nuclear magnetic resonance (NMR) investigations, which included 1H and 13C NMR. Molecular docking studies predicted the free binding energy of the four triterpenes inside the steroid binding pocket of Mycobacterium tuberculosis fadA5 thiolase compared to a reported inhibitor. Thus, their ability to inhibit the growth of M. tuberculosis was predicted and was confirmed to possess significant antimycobacterial activity when tested against Mycobacterium smegmatis, M. tuberculosis H37Rv (ATCC 25177), clinical isolates of multi-drug-resistant M. tuberculosis (MDR-TB) and extensively drug-resistant M. tuberculosis (XDR-TB) using the Micro Alamar Blue Assay. Ursolic acid was isolated from this plant for the first time.
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    Synthesis, polymorphism, and insecticidal activity of Methyl 4-(4-chlorophenyl)-8-iodo-2-methyl-6-oxo-1,6-dihydro-4H-pyrimido[2,1-b]quinazoline-3-Carboxylate against Anopheles arabiensis mosquito.
    (Wiley Online Library, 2016-07) Venugopala, Katharigatta Narayanaswamy; Nayak, Susanta K.; Gleiser, Raquel M.; Sanchez-Borzone, M. E.; Garcia, D. A.; Odhav, Bharti
    Mosquitoes are the major vectors of pathogens and parasites including those causing malaria, the most deadly vector-borne disease. The negative environmental effects of most synthetic compounds combined with widespread development of insecticide resistance encourage an interest in finding and developing alternative products against mosquitoes. In this study, pyrimido[2,1-b]quinazoline derivative DHPM3 has been synthesized by three-step chemical reaction and screened for larvicide, adulticide, and repellent properties against Anopheles arabiensis, one of the dominant vectors of malaria in Africa. The title compound emerged as potential larvicide agent for further research and development, because it exerted 100% mortality, while adulticide activity was considered moderate.
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    The chemical composition of leaf essential oils of Psidium guajava L. (white and pink fruit forms) from South Africa
    (Taylor and Francis, 2015-02-23) Chalannavar, Raju K.; Venugopala, Katharigatta Narayanaswamy; Baijnath, Himansu; Odhav, Bharti
    The leaf oils of Psidium guajava (white fruit) and Psidium guajava (pink fruit) collected in KwaZulu-Natal province of South Africa has been examined by Gas chromatography-Mass spectrometry (GC-MS), and the apparent concentrations were determined by gas chromatography with a flame ionization detector. A total of twenty compounds of 88.9 % from white fruit and forty eight compounds representing 97.5 % from pink fruit of the oils were identified. P. guajava (white fruit) produced oil that was much richer in hydrocarbons (38.8 %), sesquiterpenes hydrocarbons (24.0 %), oxygenated sesquiterpenes (19.1 %) and alcohol (6.8 %). The major constituents of the essential oil were caryophyllene oxide (14.0 %), caryophyllene (13.9 %), 1H-cycloprop[e]azulene (11.6 %), adamantane (9.4 %), 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol (6.8 %), α-cubebene (6.7 %), 1,2,3,4-tetrahydronaphthalene (3.9 %), β-humulene (3.5 %), 1,2,4a,5,6,8a-hexahydronaphthalene (3.2 %) and α-caryophyllene (3.0 %). The leaf oil of P. guajava (pink fruit) contained a mixture of hydrocarbons (30.5 %), sesquiterpene hydrocarbons (25.4 %), alcohol (24.4 %) and oxygenated sesquiterpenes (15.0 %). The major constituents of the essential oil were caryophyllene oxide (13.0 %), tetracyclo[6.3.2.0(2,5).0(1,8)]tridecan-9-ol (12.9 %), caryophyllene (9.5 %), 3,7,11-trimethyl-1,6,10-dodecatrien-3-ol (9.5 %), 1H-cycloprop[e]azulene (8.1 %), Z-3-hexadecen-7-yne (4.6 %) and eudesma-4(14),11-diene (4.1 %). High concentration of caryophyllene oxide and caryophyllene in both the oils suggests its usefulness as natural preservatives in the food industry. The terpenic and ester compounds could contribute to the unique flavor of P. guajava leaves.